Journal articles on the topic 'MiR-204'
To see the other types of publications on this topic, follow the link: MiR-204.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'MiR-204.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Huang, Zhengbiao, and Tianling Deng. "miR-204-3p Regulates Glioma Cell Biological Behaviors via Targeting Protein Kinase B (AKT1)." Journal of Biomaterials and Tissue Engineering 12, no. 12 (December 1, 2022): 2395–400. http://dx.doi.org/10.1166/jbt.2022.3188.
Full textAbstract:
This study assesses miR-204-3p’s role in glioma. Cells were transfected with miR-204-3pmimics, miR-204-3p inhibitor, or si-AKT1 to measure cell proliferation, invasion, migration and apoptosis. Glioma tissues showed a significantly downregulated miR-204-3p, whose knockdown can significantly promote cell proliferation, migration and invasion. However, all the above changes or cell behavior were inhibited by overexpression of miR-204-3p. miR-204-3p regulated AKT1 and its silence can promote cell proliferation and decrease apoptosis by increasing AKT1 expression. However, si-AKT1 transfection inhibited cell proliferation and promote apoptosis induced by miR-204-3p knockdown. In summary, miR-204-3p regulates glioma cell biological behaviors by targeting AKT1.
2
Sun, Xueqin, Shan Su, Guoxiang Zhang, Hong Zhang, and Xiaohui Yu. "MiR-204 suppresses cell proliferation and promotes apoptosis in ovarian granulosa cells via targeting TPT1 in polycystic ovary syndrome." Biochemistry and Cell Biology 97, no. 5 (October 2019): 554–62. http://dx.doi.org/10.1139/bcb-2019-0019.
Full textAbstract:
MicroRNA (miR)-204 is known to be associated with several different diseases. Polycystic ovary syndrome (PCOS) has the highest incidence rate among the endocrine disorders in females between the ages of 18 and 44. We aimed to illustrate the miR-204 function in PCOS. MiR-204 expression levels in tissue and cell were examined through RT-qPCR. Colony formation assay and MTT assay were applied to detect the cell viability. Flow cytometry was employed to examine the apoptosis and cell cycle in cells. RNA binding protein immunoprecipitation assay and luciferase reporter assay were provided to demonstrate the direct interaction between translationally controlled tumor protein (TPT1) and miR-204. The expression of miR-204 was declined in KGN cells and ovarian cortex tissues of PCOS patients. MiR-204 enhanced the colony formation capacity and cell proliferation in KGN cells. Cell cycle and apoptosis were also influenced by miR-204. Since miR-204 has direct interaction with TPT1, TPT1 overexpression suppressed the miR-204-induced apoptosis and cell cycle alteration in KGN cells. MiR-204 inhibits the cell viability and induces apoptosis and cell cycle arrest by directly interacting with TPT1, indicating a role of miR-204 to be a potential target in the PCOS patients.
3
Wang, Zhiguo, Zehui Fang, Runzhang Lu, Hongli Zhao, Tiejun Gong, Dong Liu, Luojia Hong, Jun Ma, and Mei Zhang. "MicroRNA-204 Potentiates the Sensitivity of Acute Myeloid Leukemia Cells to Arsenic Trioxide." Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 27, no. 9 (September 23, 2019): 1035–42. http://dx.doi.org/10.3727/096504019x15528367532612.
Full textAbstract:
Although arsenic trioxide (ATO) is a well-known antileukemic drug used for acute promyelocytic leukemia treatment, the development of ATO resistance is still a big challenge. We previously reported that microRNA-204 (miR-204) was involved in the regulation of acute myeloid leukemia (AML) cell apoptosis, but its role in chemoresistance is poorly understood. In the present study, we showed that miR-204 was significantly increased in AML cells after ATO treatment. Interestingly, the increased miR-204 level that was negatively correlated with ATO induced the decrease in cell viability and baculoviral inhibition of apoptosis protein repeat-containing 6 (BIRC6) expression. Overexpression of miR-204 potentiated ATO-induced AML cell growth inhibition and apoptosis. Furthermore, miR-204 directly targets to the 3′-UTR of BIRC6. Upregulation of miR-204 decreased BIRC6 luciferase activity and expression, which subsequently enhanced the expression of p53. Restoration of BIRC6 markedly reversed the effect of miR-204 on the regulation of AML cell sensitivity to ATO. Taken together, our study demonstrates that miR-204 decreases ATO chemoresistance in AML cells at least partially via promoting BIRC6/p53-mediated apoptosis. miR-204 represents a novel target of ATO, and upregulation of miR-204 may be a useful strategy to improve the efficacy of ATO in AML treatment.
4
Du, Youyou, Guanghui Liu, Luosha Zhao, and Rui Yao. "Protective Effect of miR-204 on Doxorubicin-Induced Cardiomyocyte Injury via HMGB1." Oxidative Medicine and Cellular Longevity 2020 (November 19, 2020): 1–16. http://dx.doi.org/10.1155/2020/8819771.
Full textAbstract:
The toxicity of doxorubicin (DOX) limits its clinical application. Nevertheless, at present, there is no effective drug to prevent DOX-induced cardiac injury. miR-204 is a newly discovered miRNA with many protective effects on cardiovascular diseases. However, little research has been done on the effects of miR-204 on DOX-induced cardiac injury. Our study is aimed at investigating the effect of miR-204 on DOX-induced myocardial injury. An adenoassociated virus system was used to achieve cardiac-specific overexpression of miR-204. Two weeks later, the mice were intraperitoneally injected with DOX (15 mg/kg) to induce cardiac injury. H9c2 myocardial cells were used to validate the role of miR-204 in vitro. Our study showed that miR-204 expression was decreased in DOX-treated hearts. miR-204 overexpression improved cardiac function and alleviated cardiac inflammation, apoptosis, and autophagy induced by DOX. In addition, our results showed that miR-204 prevented DOX-induced injury in cardiomyocytes by directly decreasing HMGB1 expression. Moreover, the overexpression of HMGB1 could offset the protective effects of miR-204 against DOX-induced cardiac injury. In summary, our study showed that miR-204 protected against DOX-induced cardiac injury via the inhibition of HMGB1, and increasing miR-204 expression may be a new treatment option for patients with DOX-induced cardiac injury.
5
Song, Rui, Yufeng Zhai, Lihua Ao, David A. Fullerton, and Xianzhong Meng. "MicroRNA-204 Deficiency in Human Aortic Valves Elevates Valvular Osteogenic Activity." International Journal of Molecular Sciences 21, no. 1 (December 20, 2019): 76. http://dx.doi.org/10.3390/ijms21010076.
Full textAbstract:
Aortic valve interstitial cells (AVICs) play a major role in valvular calcification associated with calcific aortic valve disease (CAVD). Although AVICs from diseased valves display a pro-osteogenic phenotype, the underlying mechanism causing this remains unclear. MicroRNA-204 (miR-204) is a negative regulator of osteoblast differentiation. We sought to analyze miR-204 expression in diseased human aortic valves and determine the role of this miR in AVIC osteogenic activity associated with CAVD pathobiology. In situ hybridization and PCR analysis revealed miR-204 deficiency in diseased valves and in AVICs from diseased valves. MiR-204 mimic suppressed alkaline phosphatase (ALP) expression and calcium deposition in AVICs from diseased valves. MiR-204 antagomir enhanced ALP expression in AVICs from normal valves through induction of Runx2 and Osx, and expression of miR-204 antagomir in mouse aortic valves promoted calcium deposition through up-regulation of Runx2 and Osx. Further, miR-204 mimic suppressed the osteogenic responses to TGF-β1 in AVICs of normal valves. In conclusion, miR-204 deficiency contributes to the mechanism underlying elevated osteogenic activity in diseased aortic valves, and miR-204 is capable of reversing the pro-osteogenic phenotype of AVICs of diseased valves and suppressing AVIC osteogenic response to stimulation. Exogenous miR-204 may have therapeutic potential for inhibiting valvular calcification associated with CAVD progression.
6
Su, Qunxue, Hao Shen, Bei Gu, and Ning Zhu. "miR-204-5p Hampers Breast Cancer Malignancy and Affects the Cell Cycle by Targeting PRR11." Computational and Mathematical Methods in Medicine 2022 (January 27, 2022): 1–10. http://dx.doi.org/10.1155/2022/4010947.
Full textAbstract:
Purpose. To unravel mechanisms of miR-204-5p in breast cancer (BC) cells. Methods. miR-204-5p expression level in BC cell lines was measured by qRT-PCR. Putative binding sites of miR-204-5p on the 3 ′ -untranslated region of PRR11 were predicted by the bioinformatics method and verified by the dual-luciferase method. Protein and mRNA levels of PRR11 in BC were determined by western blot and qRT-PCR. The association between two genes was analyzed by correlation analysis. Cancer cell functions were evaluated through CCK8, flow cytometry, and Transwell approaches. Results. Significant downregulation of miR-204-5p was observed in BC tissue and cells. Cell functional experiments showed the inhibition of miR-204-5p on cell behaviors and cell cycle. PRR11 was the downstream target of miR-204-5p. Inhibition of RPP11 could reverse the impacts of the miR-204-5p inhibitor on cell functions of BC. Conclusion. Our study revealed that the miR-204-5p/PRPP11 axis suppressed BC progression, which may provide a novel insight into the regulatory roles of miR-204-5p.
7
Li, Liang-Qing, Dun Pan, Qun Chen, Sheng-Wei Zhang, Di-Ya Xie, Xue-Lan Zheng, and Hui Chen. "Sensitization of Gastric Cancer Cells to 5-FU by MicroRNA-204 Through Targeting the TGFBR2-Mediated Epithelial to Mesenchymal Transition." Cellular Physiology and Biochemistry 47, no. 4 (2018): 1533–45. http://dx.doi.org/10.1159/000490871.
Full textAbstract:
Background/Aims: Gastric cancer (GC) is the most common gastrointestinal malignancy, causing cancer-related deaths in East Asia. MicroRNAs (miRNAs) are small non-coding RNAs aberrantly expressed in human tumors. In this study, we aim to investigate the roles of miR-204 in the epithelial to mesenchymal transition (EMT)-associated chemosensitivity. Methods: The expression of miR-204 was detected in clinical tumor samples and GC cell lines by real time PCR. Tumor cell’s growth, invasion, and migration were measured by MTT assay, wound healing assay, and transwell invasion assay, respectively. Western blot method was used to detect the protein levels of indicated genes. Luciferase reporter assay was performed to validate the target gene of miR-204. The in vivo role of miR-204 was measured using a xenograft mouse model of GC. Results: By comparing the expressions of miR-204 in human gastric tumors and their adjacent normal tissues, it was disclosed that miR-204 was significantly downregulated in gastric tumors. Moreover, miR-204 was downregulated in multiple GC cell lines compared with normal gastric epithelial cells. Overexpression of miR-204 suppressed GC cells’ proliferation, invasion, and migration. It is noteworthy that 5-FU treatments induced miR-204 expression and suppressed TGF-β pathway. By establishment of 5-FU resistant GC cell line, it was revealed that miR-204 was significantly downregulated in 5-FU resistant GC cells, representing mesenchymal features with downregulation of epithelial marker, while mesenchymal markers were upregulated. We identified TGFBR2 as a direct target of miR-204 by Western blot method and luciferase assay in GC cells and tumor samples as well. In addition, overexpression of miR-204 sensitized GC cells to 5-FU in vitro. Xenograft experiments demonstrated that the combination of miR-204 and 5-FU efficiently inhibited tumor growth and improved survival rate of mice as well. Eventually, we illustrated the restoration of TGFBR2 in miR-204 overexpression GC cells, which recovered resistance to 5-FU treatments compared with miR-204 overexpression GC cells. Conclusion: This study describes a miRNA-based therapeutic strategy against 5-FU resistance in GC, contributing to the development of anti-chemoresistance therapeutic agents.
8
Estephan, Leonard E., Michael V. Genuardi, Chad M. Kosanovich, Michael G. Risbano, Yingze Zhang, Nancy Petro, Annie Watson, et al. "Distinct plasma gradients of microRNA-204 in the pulmonary circulation of patients suffering from WHO Groups I and II pulmonary hypertension." Pulmonary Circulation 9, no. 2 (March 28, 2019): 204589401984064. http://dx.doi.org/10.1177/2045894019840646.
Full textAbstract:
Pulmonary hypertension (PH), a heterogeneous vascular disease, consists of subtypes with overlapping clinical phenotypes. MicroRNAs, small non-coding RNAs that negatively regulate gene expression, have emerged as regulators of PH pathogenesis. The muscle-specific micro RNA (miR)-204 is known to be depleted in diseased pulmonary artery smooth muscle cells (PASMCs), furthering proliferation and promoting PH. Alterations of circulating plasma miR-204 across the trans-pulmonary vascular bed might provide mechanistic insights into the observed intracellular depletion and may help distinguish PH subtypes. MiR-204 levels were quantified at sequential pulmonary vasculature sites in 91 patients with World Health Organization (WHO) Group I pulmonary arterial hypertension (PAH) (n = 47), Group II PH (n = 22), or no PH (n = 22). Blood from the right atrium/superior vena cava, pulmonary artery, and pulmonary capillary wedge was collected. Peripheral blood mononuclear cells (PBMCs) were isolated (n = 5/group). Excretion of miR-204 by PAH-PASMCs was also quantified in vitro. In Group I patients only, miR-204 concentration increased sequentially along the pulmonary vasculature (log fold-change slope = 0.22 [95% CI = 0.06–0.37], P = 0.008). PBMCs revealed insignificant miR-204 variations among PH groups ( P = 0.12). Cultured PAH-PAMSCs displayed a decrease of intracellular miR-204 ( P = 0.0004), and a converse increase of extracellular miR-204 ( P = 0.0018) versus control. The stepwise elevation of circulating miR-204 across the pulmonary vasculature in Group I, but not Group II, PH indicates differences in muscle-specific pathobiology between subtypes. Considering the known importance of miR-204 in PH, these findings may suggest pathologic excretion of miR-204 in Group I PAH by PASMCs, thereby accounting for decreased intracellular miR-204 concentration.
9
Qu, Liangliang, Zhongqiu Li, and Pinduan Liu. "mir-204-5p Acts as a Tumor Suppressor by Targeting DNM2 in Osteosarcoma Cells." Journal of Healthcare Engineering 2022 (February 9, 2022): 1–7. http://dx.doi.org/10.1155/2022/8944588.
Full textAbstract:
Osteosarcoma is a malignant bone tumor composed of interstitial cells. We aim to seek the function of mir-204-5p/DNM2 in osteosarcoma cells. From April 2017 to August 2019, 58 cases of cancer tissues and paracancer tissues were obtained from patients with osteosarcoma in our hospital. qPCR was used to detect mir-204-5p in excisional cancer tissues and paracarcinoma tissues of osteosarcoma patients. The overexpression vector of mir-204-5p was established and transfected into osteosarcoma cells, and the propagation, invasiveness, migration, and apoptosis of osteosarcoma cells were observed. StarBase was employed to forecast the binding site of mir-204-5p and DNM2. The targeting connection of mir-204-5p with DNM2 was detected via double luciferase reporter gene. mir-204-5p was lessened in osteosarcoma ( p < 0.05 ). mir-204-5p overexpression suppressed propagation and accelerated apoptosis of osteosarcoma cells ( p < 0.05 ). The results of double luciferase reporter gene revealed that the fluorescence activity of mir-204-5p was obviously declined when binding to DNM2 ( p < 0.05 ). mir-204-5p functions as a tumor inhibitor by targeting DNM2 in osteosarcoma cells. Our research is helpful to provide new ideas for clinical treatment.
10
Cheng, Yuan, Dandan Wang, Feng Wang, Jing Liu, Baorui Huang, Maria Angeles Baker, Jianyong Yin, et al. "Endogenous miR-204 Protects the Kidney against Chronic Injury in Hypertension and Diabetes." Journal of the American Society of Nephrology 31, no. 7 (June 2, 2020): 1539–54. http://dx.doi.org/10.1681/asn.2019101100.
Full textAbstract:
BackgroundAberrant microRNA (miRNA) expression affects biologic processes and downstream genes that are crucial to CKD initiation or progression. The miRNA miR-204-5p is highly expressed in the kidney but whether miR-204-5p plays any role in the development of chronic renal injury is unknown.MethodsWe used real-time PCR to determine levels of miR-204 in human kidney biopsies and animal models. We generated Mir204 knockout mice and used locked nucleic acid–modified anti-miR to knock down miR-204-5p in mice and rats. We used a number of physiologic, histologic, and molecular techniques to analyze the potential role of miR-204-5p in three models of renal injury.ResultsKidneys of patients with hypertension, hypertensive nephrosclerosis, or diabetic nephropathy exhibited a significant decrease in miR-204-5p compared with controls. Dahl salt-sensitive rats displayed lower levels of renal miR-204-5p compared with partially protected congenic SS.13BN26 rats. Administering anti–miR-204-5p to SS.13BN26 rats exacerbated interlobular artery thickening and renal interstitial fibrosis. In a mouse model of hypertensive renal injury induced by uninephrectomy, angiotensin II, and a high-salt diet, Mir204 gene knockout significantly exacerbated albuminuria, renal interstitial fibrosis, and interlobular artery thickening, despite attenuation of hypertension. In diabetic db/db mice, administering anti–miR-204-5p exacerbated albuminuria and cortical fibrosis without influencing blood glucose levels. In all three models, inhibiting miR-204-5p or deleting Mir204 led to upregulation of protein tyrosine phosphatase SHP2, a target gene of miR-204-5p, and increased phosphorylation of signal transducer and activator of transcription 3, or STAT3, which is an injury-promoting effector of SHP2.ConclusionsThese findings indicate that the highly expressed miR-204-5p plays a prominent role in safeguarding the kidneys against common causes of chronic renal injury.
11
Liu, Jing, Yong Liu, Feng Wang, and Mingyu Liang. "miR-204: Molecular Regulation and Role in Cardiovascular and Renal Diseases." Hypertension 78, no. 2 (August 2021): 270–81. http://dx.doi.org/10.1161/hypertensionaha.121.14536.
Full textAbstract:
The field of microRNA research has evolved from studies aiming to gauge the importance of microRNAs to those focusing on understanding a subset of specific microRNAs that have emerged as potent regulators of molecular systems and pathophysiological conditions. In this article, we review the molecular features and regulation of miR-204 and the growing body of evidence for an important role of miR-204 in the regulation of cardiovascular and renal physiology and pathophysiological processes. miR-204 exhibits a highly tissue-specific expression pattern, and miR-204 abundance is regulated by several transcriptional and posttranscriptional mechanisms. Strong evidence supports a role for miR-204 in attenuating pulmonary arterial hypertension and hypertensive and diabetic renal injury while promoting hypertension and endothelial dysfunction in a wide range of model systems. miR-204 may influence these disease processes by targeting several biological pathways in a tissue-specific manner. miR-204 is dysregulated in patients with cardiovascular and renal diseases. The unequivocal functional roles and clear clinical relevance indicate that miR-204 is a high-value microRNA in cardiovascular and renal diseases.
12
Zheng, Wenhong, Wei Huang, and Xuchao Yu. "Study on Serum miR-204 Expression Levels in Patients with Severe Pneumonia and Patients with Primary Bronchial Lung Cancer and Its Diagnostic Value." Evidence-Based Complementary and Alternative Medicine 2021 (October 12, 2021): 1–7. http://dx.doi.org/10.1155/2021/6034413.
Full textAbstract:
Objective. To analyze the expression and clinical significance of miR-204 in the serum of patients with severe pneumonia (SP) and primary bronchial lung cancer (LC). Methods. 65 SP patients and 43 primary bronchial LC patients who were treated in the hospital from January 2017 to December 2018 were randomly selected as the SP group and LC group. At the same time, healthy patients from the physical examination department of the hospital were selected. 65 cases were the control group. QRT-PCR detected serum miR-204 expression and compared the differences between groups. The pathological data of patients were collected, and the relationship between serum miR-204 and the patient’s pathological data was compared; the area under the ROC curve and Kaplan–Meier curve were used to evaluate the diagnostic value of serum miR-204 for the two conditions and to explore the relationship between serum miR-204 and prognosis. Results. The serum miR-204 of the SP group was (0.43 ± 0.09), the serum miR-204 of the LC group was (0.40 ± 0.10), the serum miR-204 of the control group was (1.00 ± 0.09), and the miR-204 level of was significantly higher than that of the control group, and the difference between the groups was statistically significant ( P < 0.05). There was no significant difference in serum miR-204 levels between the SP group and the LC group ( P > 0.05). Serum miR-204 levels in SP patients with cumulative organs ≥3 were higher than those with cumulative organs <3, and the difference was statistically significant ( P < 0.001). In the LC group, in patients with stage III to IV and low and undifferentiated patients, the level of miR-204 was higher than that of stage I∼II and high and moderately differentiated patients, and the difference was statistically significant ( P < 0.001). The level of miR-204 in the two groups of patients (0.89 ± 0.10, 0.83 ± 0.13) who died of illness was significantly higher than that of the surviving patients (1.00 ± 0.11, 1.00 ± 0.10), and the difference was statistically significant ( P < 0.05); the survival rate of patients with high expression of miR-204 was higher than that of patients with low expression. The AUC of serum miR-204 level to SP and LC was 0.766 and 0.818, respectively. Conclusion. The level of miR-204 in the serum of SP patients and patients with primary bronchial LC was significantly lower than that of healthy people, and patients who died were lower than those who survived; the miR-204 in serum has a good diagnostic value for SP and LC and is related to the survival and prognosis of patients.
13
Lapkina, E. Z., N. V. Palkinа, A. S. Averchuk, A. R. Esimbekova, and T. G. Ruksha. "Antitumor, toxicity and target gene expression evaluation of MiR-204-5p mimic application on melanoma b16-bearing mice." Siberian journal of oncology 21, no. 3 (June 29, 2022): 61–69. http://dx.doi.org/10.21294/1814-4861-2022-21-3-61-69.
Full textAbstract:
Objective. To evaluate anti-tumor, toxic effect of miR-204-5p mimic applicaton on melanoma B-16-bearing mice followed by miR-204-5p target gene expression estimation in melanoma tumor and distant organs. Material and Methods. C57Bl/6 melanoma B-16-bearing mice were used. The animals of the experimental group were intraperitoneally injected with a 5 nM miR-204-5p miRNA simulator (mimic) on the 8th, 10th, and 12th days after melanoma B-16 cell transplantation. Based on the results of bioinformatic analysis, miR-204-5p target genes BCL2 and SIRT1 expression levels were determined by quantitative real-time PCR. The toxic effect of miR-204-5p mimic was estimated by the evaluation of body weight, mass of the internal organs, and motor activity. Results. On the 13-14th days of the experiment, the motor activity of animals in the control groups decreased signifcantly compared to the group of animals treated by miR-204-5p. Target gene BCL2 showed increased expression in the lungs and kidneys and SIRT1 levels were increased in the lungs of miR-204-5p mimic treated animals (p˂0.05). Tumor mass tended to decrease in the animals treated by miR-204-5p mimic. Conclusion. Modulation of the level of miR-204-5p microRNA led to changes in the expression of SIRT1 and BCL2 in the lungs of animals, and changes in the expression of BCL2in the kidneys. MiR-204-5p mimic application did not have toxic effect on animals treated. Further studies are necessary to clarify miR-204-5p implication in melanoma cell proliferation regulation as well as it’s biodistibution in the tumor tissue.
14
Courboulin, Audrey, Roxane Paulin, Nellie J. Giguère, Nehmé Saksouk, Tanya Perreault, Jolyane Meloche, Eric R. Paquet, et al. "Role for miR-204 in human pulmonary arterial hypertension." Journal of Experimental Medicine 208, no. 3 (February 14, 2011): 535–48. http://dx.doi.org/10.1084/jem.20101812.
Full textAbstract:
Pulmonary arterial hypertension (PAH) is characterized by enhanced proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs). Because microRNAs have been recently implicated in the regulation of cell proliferation and apoptosis, we hypothesized that these regulatory molecules might be implicated in the etiology of PAH. In this study, we show that miR-204 expression in PASMCs is down-regulated in both human and rodent PAH. miR-204 down-regulation correlates with PAH severity and accounts for the proliferative and antiapoptotic phenotypes of PAH-PASMCs. STAT3 activation suppresses miR-204 expression, and miR-204 directly targets SHP2 expression, thereby SHP2 up-regulation, by miR-204 down-regulation, activates the Src kinase and nuclear factor of activated T cells (NFAT). STAT3 also directly induces NFATc2 expression. NFAT and SHP2 were needed to sustain PAH-PASMC proliferation and resistance to apoptosis. Finally, delivery of synthetic miR-204 to the lungs of animals with PAH significantly reduced disease severity. This study uncovers a new regulatory pathway involving miR-204 that is critical to the etiology of PAH and indicates that reestablishing miR-204 expression should be explored as a potential new therapy for this disease.
15
Zhang, Congxiao, Kiyoharu J. Miyagishima, Lijin Dong, Aaron Rising, Malika Nimmagadda, Genqing Liang, Ruchi Sharma, et al. "Regulation of phagolysosomal activity by miR-204 critically influences structure and function of retinal pigment epithelium/retina." Human Molecular Genetics 28, no. 20 (July 23, 2019): 3355–68. http://dx.doi.org/10.1093/hmg/ddz171.
Full textAbstract:
Abstract MicroRNA-204 (miR-204) is expressed in pulmonary, renal, mammary and eye tissue, and its reduction can result in multiple diseases including cancer. We first generated miR-204−/− mice to study the impact of miR-204 loss on retinal and retinal pigment epithelium (RPE) structure and function. The RPE is fundamentally important for maintaining the health and integrity of the retinal photoreceptors. miR-204−/− eyes evidenced areas of hyper-autofluorescence and defective photoreceptor digestion, along with increased microglia migration to the RPE. Migratory Iba1+ microglial cells were localized to the RPE apical surface where they participated in the phagocytosis of photoreceptor outer segments (POSs) and contributed to a persistent build-up of rhodopsin. These structural, molecular and cellular outcomes were accompanied by decreased light-evoked electrical responses from the retina and RPE. In parallel experiments, we suppressed miR-204 expression in primary cultures of human RPE using anti-miR-204. In vitro suppression of miR-204 in human RPE similarly showed abnormal POS clearance and altered expression of autophagy-related proteins and Rab22a, a regulator of endosome maturation. Together, these in vitro and in vivo experiments suggest that the normally high levels of miR-204 in RPE can mitigate disease onset by preventing generation of oxidative stress and inflammation originating from intracellular accumulation of undigested photoreactive POS lipids. More generally, these results implicate RPE miR-204-mediated regulation of autophagy and endolysosomal interaction as a critical determinant of normal RPE/retina structure and function.
16
Dong, Ning. "Long Noncoding RNA NEAT1 Regulates TGF-β2-Induced Epithelial-Mesenchymal Transition of Lens Epithelial Cells through the miR-34a/Snail1 and miR-204/Zeb1 Pathways." BioMed Research International 2020 (June 1, 2020): 1–19. http://dx.doi.org/10.1155/2020/8352579.
Full textAbstract:
The aim of this study was to explore whether the long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1)/miR-34a/Snail1 and NEAT1/miR-204/Zeb1 pathways are involved in epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). Primary human LECs (HLECs) were separated and cultured. Our results identified that TGF-β2 induces NEAT1 overexpression in a dose-dependent manner and a time-dependent manner. Additionally, TGF-β2 induced downregulation of E-cadherin and upregulation of fibronectin in primary HLECs through a NEAT1-dependent mechanism. Microarray analysis showed that NEAT1 overexpression inhibited the miR-34a and miR-204 levels in the LECs. The expression of miR-34a and miR-204 was decreased, and the levels of Snail1 and Zeb1 were elevated in human posterior capsule opacification- (PCO-) attached LECs and the LECs obtained from anterior subcapsular cataract (ASC) by quantitative RT-PCR (qRT-PCR). Mechanistic studies revealed that NEAT1 negatively regulates miR-34a or miR-204, and miR-34a or miR-204 directly targets Snail1 or Zeb1 by luciferase assay and RNA-binding protein immunoprecipitation assay, respectively. Overall, the NEAT1/miR-34a/Snail1 and NEAT1/miR-204/Zeb1 pathways are involved in TGF-β2-induced EMT of HLECs. In summary, TGF-β2 induces NEAT1 overexpression, which in turn suggests that NEAT1 acts as a ceRNA targeting Snail1 or Zeb1 by binding miR-34a or miR-204, and promotes the progression of EMT of LECs.
17
Yan, Hongliang, Weiguang Wu, Hongyu Ge, Pengfei Li, and Zheng Wang. "Up-Regulation of miR-204 Enhances Anoikis Sensitivity in Epithelial Ovarian Cancer Cell Line Via Brain-Derived Neurotrophic Factor Pathway In Vitro." International Journal of Gynecologic Cancer 25, no. 6 (July 2015): 944–52. http://dx.doi.org/10.1097/igc.0000000000000456.
Full textAbstract:
ObjectiveGenomic loci encoding miR-204, which was predicted to target brain-derived neurotrophic factor (BDNF), were frequently lost in multiple cancer, including epithelial ovarian cancer (EOC). In this study, we aimed to find out the influence of miR-204 expression level on EOC cell anoikis sensitivity and to explore possible mechanisms of this process.MethodsFirst, we screened EOC cells, which maintain anoikis resistance forming an anoikis pattern. miR-204 expression level and apoptosis were measured, respectively, by quantitative reverse transcriptase polymerase chain reaction and Annexin-V–R-PE/7-amino-actinomycin assay. Then we restored the expression level of miR-204 by transfection with pre–miR-204. miR-204 expression level and apoptosis were measured as before; cell invasion and migration ability were detected by transwell invasion assay and wound-healing assay. The messenger RNA level of BDNF was also detected by quantitative reverse transcriptase polymerase chain reaction; Western blot analysis was performed to assess pAKT expression.ResultsExpression of miR-204 is significantly down-regulated in an anoikis pattern. Restored expression level of miR-204 enables cells to acquire more sensitivity to anoikis and decrease invasive and metastatic behavior, and also results in BDNF down-expression and inhibits activation of mitochondria-dependent pathway through the PI3K/AKT signaling pathway leading to cancer cell anoikis in EOC cells.ConclusionsmiR-204 up-regulation may be linked directly to the sensitivity of EOC cell anoikis by contributing to BDNF down-regulation. Our findings provide a novel mechanism for manipulating miR-204 levels therapeutically to restore anoikis sensitivity.
18
Wang, Na, Yuliang Yuan, Shipeng Sun, and Guijian Liu. "microRNA-204-5p participates in atherosclerosis via targeting MMP-9." Open Medicine 15, no. 1 (March 26, 2020): 231–39. http://dx.doi.org/10.1515/med-2020-0034.
Full textAbstract:
AbstractThe aim of the present study was to investigate the role and mechanism of microRNA-204-5p (miR-204-5p) in atherosclerosis (AS)-related abnormal human vascular smooth muscle cells (hVSMCs) function. Firstly, we analyzed the expression of miR-204-5p and found that the miR-204-5p expression level was clearly downregulated in atherosclerotic plaque tissues and blood samples compared to the normal controls. Then, matrix metallopeptidase-9 (MMP-9) was predicted to be the potential target of miR-204-5p by TargetScan and this prediction was confirmed by luciferase assays. Besides, we observed that miR-204-5p could negatively regulate the expression of MMP-9 in hVSMCs. Subsequently, Thiazolyl Blue Tetrazolium Bromide (MTT) assay, transwell assay and flow cytometry were performed to detect the proliferation, migration and apoptosis of hVSMCs. Down-expression of miR-204-5p led to the promotion of proliferation and migration accompanied with the suppression of apoptosis in hVSMCs, and these effects were reversed by MMP-9-siRNA. In addition, overexpressed miR-204-5p could inhibit hVSMC proliferation and migration and promote the apoptosis of hVSMCs. However, the effects were also abrogated by overexpressed MMP-9. Together, our findings showed that miR-204-5p plays an important role in the growth and migration of hVSMCs by targeting MMP-9, which might be a novel biomarker and promising therapeutic target for AS.
19
Tan, Ya, Linyuan Shen, Mailin Gan, Yuan Fan, Xiao Cheng, Ting Zheng, Lili Niu, et al. "Downregulated miR-204 Promotes Skeletal Muscle Regeneration." BioMed Research International 2020 (November 17, 2020): 1–9. http://dx.doi.org/10.1155/2020/3183296.
Full textAbstract:
Skeletal muscle is the most abundant and a highly plastic tissue of the mammals, especially when it comes to regenerate after trauma, but there is limited information about the mechanism of muscle repair and its regeneration. In the present study, we found that miR-204 is downregulated after skeletal muscle injury. In vitro experiments showed that over-expression of miR-204 by transfecting with miR-204 mimics suppressed C2C12 cell proliferation, migration, and blocked subsequent differentiation, whereas inhibition of miR-204 by transfecting with miR-204 inhibitor showed the converse effects. Furthermore, through the dual luciferase reporter system, we demonstrated that miR-204 can target the 3’UTR regions of Pax7, IGF1, and Mef2c and inhibit their expression. Taken together, our results suggest that Pax7, IGF1, and Mef2c are the target genes of miR-204 in the process of myoblasts proliferation, cell migration, and differentiation, respectively, and may contribute to mouse skeletal muscle regeneration. Our results may provide new ideas and references for the skeletal muscle study and may also provide therapeutic strategies of skeletal muscle injury.
20
Hu, Liangliang, Helena Kolibaba, Siyou Zhang, Minhua Cao, Huihui Niu, Haoyan Mei, Yaming Hao, Yang Xu, and Qinan Yin. "MicroRNA-204-5p Inhibits Ovarian Cancer Cell Proliferation by Down-Regulating USP47." Cell Transplantation 28, no. 1_suppl (September 17, 2019): 51S—58S. http://dx.doi.org/10.1177/0963689719877372.
Full textAbstract:
Ovarian cancer (OC) is the most lethal gynecologic cancer, and the incidence of OC has risen steadily worldwide. Numerous microRNAs (miRNAs) have been found to be involved in the progression of OC. miR-204-5p is down-regulated and functions as a tumor suppressor in various types of human malignant tumors. However, the biological roles and molecular mechanisms of miR-204-5p in OC still remain unclear. In this study, the aberrant down-regulation of miR-204-5p was detected in OC tissues. We also observed that miR-204-5p overexpression represses OC cell proliferation. Ubiquitin-specific peptidase 47 (USP47) is verified as the functional target of miR-204-5p, through which it plays an important biological role in OC. Our results uncover new functions and mechanisms for miR-204-5p in the progression of OC, and provide a potential therapeutic target for the treatment of OC.
21
Chen, Dabing, Tingting Xiao, Dandan Lin, Haojie Zhu, Jingjing Xu, Xiaofeng Luo, Jinhua Ren, et al. "DNA Methylation-Mediated Silencing of Mir-204 Enhances the Occurrence of T-Cell Acute Lymphoblastic Leukemia By Upregulating MMP-2 and MMP-9 through the NF-Κb Signaling Pathway." Blood 136, Supplement 1 (November 5, 2020): 11. http://dx.doi.org/10.1182/blood-2020-142386.
Full textAbstract:
Background : MicroRNAs (miR) are non-coding RNAs that play a role in regulation multiple functions in different cell types. Previous studies have shown that miR-204 is downregulated in T-ALL. We previously reported that matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) gene polymorphisms may be associated with the risk of T-cell acute lymphoblastic leukemia (T-ALL). The present study aims to decipher the role of miR-204 and MMP-2/MMP-9 in T-ALL occurrence to guide the diagnosis and treatment of T-ALL in the clinics. Methods: Expression of miR-204 was determined in the bone marrow and peripheral blood samples from 70 T-ALL patients and 70 healthy volunteers by real-time quantitative PCR (RT-qPCR). Bisulfite sequencing PCR (BSP) was used to detect the DNA methylation levels of the miR-204 promoter region in T-ALL patients and T-ALL cell lines.The effect of miR-204 on cell proliferation was evaluated with the cell counting kit-8 solution (CCK-8) assay and by Hoechst and PI double staining. The binding site of miR-204 on IRAK1 was predicted by the Primer Premier 5.0 and the defined binding sequences were used to construct luciferase-tag plasmids. The regulation of IRAK1 expression by miR-204 was evaluated by RT-qPCR and Western blot analysis. With the purpose to confirm the role of MMP-2 and MMP-9 in the occurrence of T-ALL, we investigated the effect of related proteins on T-ALL cells using Western blot. To determine that miR-204 affects the occurrence of T-ALL disease by regulating the NF-KB signaling pathway, RT-qPCR and Western Blot were used for verification. Results: DNA methylation directly affects the miR-204 expression in the promoter region when T-ALL developed. Moreover, overexpression of miR-204 inhibited the proliferation and enhanced the apoptosis of T-ALL cells. Notably, overexpression of miR-204 inhibited IRAK1, which in turn inhibited the proliferation and enhanced the apoptosis of T-ALL cells. Furthermore, IRAK1 enhanced the expression of MMP-2 and MMP-9 through phosphorylation of of p65 NF-κB, and miR-204 modulated MMP-2 and MMP-9 expression through the IRAK1/NF-κB signaling pathway. Conclusion s : Our results demonstrate that in T-ALL cells, DNA methylation-mediated silencing of miR-204 regulates the expression of MMP-2 and MMP-9 through increased transcription of IRAK1, and activation of the NF-κB signaling pathway. These data provide a potential mechanism for the role of MMP-2 and MMP-9 in the occurrence of T-ALL. Further studies will be needed to demonstrate whether demethylation of miR-204 may be a promising treatment for T-ALL. Disclosures No relevant conflicts of interest to declare.
22
Dalle Carbonare, Luca, Jessica Bertacco, Arianna Minoia, Mattia Cominacini, Lekhana Bhandary, Rossella Elia, Giovanni Gambaro, Monica Mottes, and Maria Teresa Valenti. "Modulation of miR-204 Expression during Chondrogenesis." International Journal of Molecular Sciences 23, no. 4 (February 15, 2022): 2130. http://dx.doi.org/10.3390/ijms23042130.
Full textAbstract:
RUNX2 and SOX9 are two pivotal transcriptional regulators of chondrogenesis. It has been demonstrated that RUNX2 and SOX9 physically interact; RUNX2 transactivation may be inhibited by SOX9. In addition, RUNX2 exerts reciprocal inhibition on SOX9 transactivity. Epigenetic control of gene expression plays a major role in the alternative differentiation fates of stem cells; in particular, it has been reported that SOX9 can promote the expression of miRNA (miR)-204. Our aim was therefore to investigate the miR-204-5p role during chondrogenesis and to identify the relationship between this miR and the transcription factors plus downstream genes involved in chondrogenic commitment and differentiation. To evaluate the role of miR-204 in chondrogenesis, we performed in vitro transfection experiments by using Mesenchymal Stem Cells (MSCs). We also evaluated miR-204-5p expression in zebrafish models (adults and larvae). By silencing miR-204 during the early differentiation phase, we observed the upregulation of SOX9 and chondrogenic related genes compared to controls. In addition, we observed the upregulation of COL1A1 (a RUNX2 downstream gene), whereas RUNX2 expression of RUNX2 was slightly affected compared to controls. However, RUNX2 protein levels increased in miR-204-silenced cells. The positive effects of miR204 silencing on osteogenic differentiation were also observed in the intermediate phase of osteogenic differentiation. On the contrary, chondrocytes’ maturation was considerably affected by miR-204 downregulation. In conclusion, our results suggest that miR-204 negatively regulates the osteochondrogenic commitment of MSCs, while it positively regulates chondrocytes’ maturation.
23
Yuan, Xiao, Shuanhu Wang, Mulin Liu, Zhen Lu, Yanqing Zhan, Wenbin Wang, and A.-Man Xu. "Histological and Pathological Assessment of miR-204 and SOX4 Levels in Gastric Cancer Patients." BioMed Research International 2017 (2017): 1–8. http://dx.doi.org/10.1155/2017/6894675.
Full textAbstract:
Gastric cancer is one of the most common cancers and the efficient therapeutic methods are limited. Further study of the exact molecular mechanism of gastric cancer to develop novel targeted therapies is necessary and urgent. We herein systematically examined that miR-204 suppressed both proliferation and metastasis of gastric cancer AGS cells. miR-204 directly targeted SOX4. In clinical tissue research, we determined that miR-204 was expressed much lower and SOX4 expressed much higher in gastric cancer tissues compared with normal gastric tissues. Associated analysis with clinicopathological parameters in gastric cancer patients showed miR-204 was associated with no lymph node metastasis and early tumor stages whereas SOX4 was associated with lymph node metastasis and advanced tumor stages. In addition, miR-204 and SOX4 were negatively correlated in tissues from gastric cancer patients. Our findings examined the important role of miR-204 and SOX4 played in gastric cancer, and they could be used as candidate therapeutic targets for gastric cancer therapy.
24
Liu, Hong, Ansheng Cai, Zhiying Li, Haifang Ma, Limiung Fan, Jinghong Ma, and Danhua Zhao. "MicroRNA-204 Attenuates Oxidative Damage in Cardiac Stem Cell Through Regulation of Bone Marrow Stromal Cell (BMSC) Adipogenic and Osteogenic Differentiation." Journal of Biomaterials and Tissue Engineering 11, no. 11 (November 1, 2021): 2203–9. http://dx.doi.org/10.1166/jbt.2021.2802.
Full textAbstract:
Exosomes (exo) derived from bone marrow mesenchymal stem cells (BMSCs) are known to promote cell growth through delivering multiple kinds of bioactive molecule including microRNAs (miR-NAs). This study aimed to explore the mechanism underlying miR-204 secreted by exo interacting oxidative damage of cardiac stem cell (CSCs). Exosomes were extracted from BMSCs (BMSC-exo) and characterized by immunofluorescence and electron microscope, while BMSC-exo were internalized by CSCs. ARS and ALP staining confirmed the mineralization of BMSCs and osteogenic and adipogenic differentiation of BMSCs. Then BMSCs were cultured in ordinary culture medium (OM) and normal medium. RT-qPCR identified miR-204 level in BMSCs disposed by OM was about five times as that of controls. miR-204 was up-regulated in the osteogenic differentiation of CSCs. Functional experiment revealed up-regulation of miR-204 inhibited the BMSC adipogenic differentiation with decreased ROS and MDA expression and elevated SOD level in the CSCs. Treatment with BMSC-exos or miR-204 up-regulation alleviated oxidative damage of CSCs. Collectively, miR-204 attenuates the oxidative damage of CSCs through regulating BMSC adipogenic and osteogenic differentiation.
25
Garcia, Alix, Sylvie Dunoyer-Geindre, Séverine Nolli, Catherine Strassel, Jean-Luc Reny, and Pierre Fontana. "miR-204-5p and Platelet Function Regulation: Insight into a Mechanism Mediated by CDC42 and GPIIbIIIa." Thrombosis and Haemostasis 121, no. 09 (May 3, 2021): 1206–19. http://dx.doi.org/10.1055/a-1497-9649.
Full textAbstract:
Abstract Background Several platelet-derived microRNAs are associated with platelet reactivity (PR) and clinical outcome in cardiovascular patients. We previously showed an association between miR-204-5p and PR in stable cardiovascular patients, but data on functional mechanisms are lacking. Aims To validate miR-204-5p as a regulator of PR in platelet-like structures (PLS) derived from human megakaryocytes and to address mechanistic issues. Methods Human hematopoietic stem cells were differentiated into megakaryocytes, enabling the transfection of miR-204-5p and the recovery of subsequent PLS. The morphology of transfected megakaryocytes and PLS was characterized using flow cytometry and microscopy. The functional impact of miR-204-5p was assessed using a flow assay, the quantification of the activated form of the GPIIbIIIa receptor, and a fibrinogen-binding assay. Quantitative polymerase chain reaction and western blot were used to evaluate the impact of miR-204-5p on a validated target, CDC42. The impact of CDC42 modulation was investigated using a silencing strategy. Results miR-204-5p transfection induced cytoskeletal changes in megakaryocytes associated with the retracted protrusion of proPLS, but it had no impact on the number of PLS released. Functional assays showed that the PLS produced by megakaryocytes transfected with miR-204-5p were more reactive than controls. This phenotype is mediated by the regulation of GPIIbIIIa expression, a key contributor in platelet–fibrinogen interaction. Similar results were obtained after CDC42 silencing, suggesting that miR-204-5p regulates PR, at least in part, via CDC42 downregulation. Conclusion We functionally validated miR-204-5p as a regulator of the PR that occurs through CDC42 downregulation and regulation of fibrinogen receptor expression.
26
Yu, Yuhui, Yongsheng Wang, Xiangying Xiao, Wei Cheng, Liqiang Hu, Weiyun Yao, Zhangxuan Qian, and Wei Wu. "MiR-204 inhibits hepatocellular cancer drug resistance and metastasis through targeting NUAK1." Biochemistry and Cell Biology 97, no. 5 (October 2019): 563–70. http://dx.doi.org/10.1139/bcb-2018-0354.
Full textAbstract:
Liver cancer is a leading cause of cancer-related deaths globally. Tumor response rate of liver cancer patients towards systemic chemotherapy is low and chemoresistance can easily develop. Identifying novel molecules that can repress drug resistance and metastasis of liver cancer will facilitate the development of new therapeutic strategies. The aim of this study is to determine the roles of NUAK1 and miR-204 in the drug resistance and metastasis of liver cancer and to reveal their relationship. We found that NUAK1 was increased in the tumor of primary liver cancer. Knockdown of NUAK1 significantly inhibited cell growth and migration. Moreover, NUAK1 was the direct downstream target of miR-204, and there was clinical relevance between miR-204 down-regulation and NUAK1 up-regulation in liver cancer. Furthermore, we found that miR-204 increased drug sensitivity by down-regulating NUAK1 expression. Based on these results, we identified miR-204 as a tumor suppressor by inhibiting NUAK1 expression in liver cancer, indicating both miR-204 and NUAK1 may act as promising targets for liver cancer therapy.
27
Yang, Yang, Jing Zhou, Wei hong Li, Zhi xiong Zhou, and Xiao bo Xia. "LncRNA NEAT1 regulated diabetic retinal epithelial-mesenchymal transition through regulating miR-204/SOX4 axis." PeerJ 9 (July 23, 2021): e11817. http://dx.doi.org/10.7717/peerj.11817.
Full textAbstract:
Aim Epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells is the key of the development of diabetic retinopathy (DR), and lncRNA NEAT1 could accelerate EMT in diabetic nephropathy. Meanwhile, as a diabetes susceptibility gene, whether sex-determining region Y-related (SRY) high-mobility group box 4 (SOX4) has relationship with lncRNA NEAT1 in DR remains unclear. Methods Firstly, NEAT1, SOX4 and miR-204 were evaluated by qRT-PCR (quantitative reverse-transcriptase PCR) under high glucose condition. Then, cell viability, proliferation, migration and invasion were respectively detected by MTT, BrdU staining, wound healing and transwell assay after NEAT1 knockdown or miR-204 overexpression. Also, the EMT-related proteins were examined by western blot and cell immunofluorescence assay. In order to confirm the relationship between miR-204 and NEAT1 or SOX4, dual luciferase reporter gene assay was conducted. At the same time, the protein levels of SOX4 and EMT-related proteins were investigated by immunohistochemistry in vivo. Results High glucose upregulated NEAT1 and SOX4 and downregulated miR-204 in ARPE19 cells. NEAT1 knockdown or miR-204 overexpression inhibited the proliferation and EMT progression of ARPE19 cells induced by high glucose. NEAT1 was identified as a molecular sponge of miR-204 to increase the level of SOX4. The effect of NEAT1 knockdown on the progression of EMT under high glucose condition in ARPE19 cells could be reversed by miR-204 inhibitor. Also, NEAT1 knockdown inhibited retinal EMT in diabetic mice. Conclusion NEAT1 regulated the development of EMT in DR through miR-204/SOX4 pathway, which could provide reference for clinical prevention and treatment.
28
Wang, Qing, Kai Li, and Xiaoliang Li. "Knockdown of LncRNA LINC00958 Inhibits the Proliferation and Migration of NSCLC Cells by MiR-204-3p/KIF2A Axis." Cell Transplantation 30 (January 1, 2021): 096368972110255. http://dx.doi.org/10.1177/09636897211025500.
Full textAbstract:
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Increasing evidence suggests that long non-coding RNAs (lncRNAs) function in the tumorigenesis of NSCLC. LINC00958, a newly identified lncRNA, has been reported to be closely linked to tumorigenesis in several cancers. However, its specific role in NSCLC remains unclear. In this study, we determined the expression of LINC00958 in NSCLC by RT-qPCR analysis and evaluated cell proliferation and migration by CCK-8 and transwell assays, respectively. We established a xenograft tumor model to examine the effect of LINC00958 on tumor growth in vivo. Luciferase reporter assays were performed to determine the interaction between LINC00958 and miR-204-3p and the interaction between miR-204-3p and KIF2A. We found that LINC00958 was up-regulated in NSCLC tissues and cell lines. Down-regulation of LINC00958 inhibited cell proliferation and migration in vitro and suppressed tumor growth in vivo. Besides, miR-204-3p was identified as a target of LINC00958 and miR-204-3p inhibitor could reverse the inhibitory effect of LINC00958 knockdown on proliferation and migration of NSCLC cells. We also validated that KIF2A, a direct target of miR-204-3p, was responsible for the biological role of LINC00958. KIF2A antagonized the effect of miR-204-3p on NSCLC cell proliferation and migration and was regulated by LINC00958/miR-204-3p. Taken together, these data indicate that the LINC00958/miR-204-3p/KIF2A axis is critical for NSCLC progression, which might provide a potential therapeutic target of NSCLC.
29
Ji, Dejiang, Yan Qiao, Xiaoping Guan, and Tao Zhang. "Serum miR-204 and miR-451 Expression and Diagnostic Value in Patients with Pulmonary Artery Hypertension Triggered by Congenital Heart Disease." Computational and Mathematical Methods in Medicine 2022 (June 13, 2022): 1–7. http://dx.doi.org/10.1155/2022/9430708.
Full textAbstract:
Objective. To determine the level of expression and clinical importance of serum miR-204 and miR-451 in patients with pulmonary arterial hypertension caused by congenital heart disease (CHD-PAH). Methods. From July 2019 to January 2021, 114 infants with congenital heart disease (CHD) were hospitalized at Qingdao’s Fuwai Cardiovascular Hospital. They were grouped into categories: CHD (53 cases) and CHD-PAH (61 cases) based on whether they had pulmonary hypertension (PAH). In addition, 60 healthy children were selected as the control group. All children underwent routine biochemical examination, echocardiography, and pulmonary arterial pressure examination. By using an enzyme-linked immunosorbent assay (ELISA), the levels of brain natriuretic peptide (BNP) and asymmetric dimethylarginine (ADMA) in the blood were measured. Additionally, reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression levels of miR-204 and miR-451 in peripheral blood. The correlation between miR-204, miR-451, BNP, ADMA, and mPAP was investigated using Pearson correlation analysis. Results. Consequently, the TC, BNP, and ADMA serum levels were considerably higher in the CHD and CHD-PAH groups than in the control group ( P < 0.05 ), whereas BNP and ADMA serum levels were significantly higher in the CHD-PAH group than in the CHD group ( P < 0.05 ). According to RT-PCR data, the expression levels of miR-204 and miR-451 in the peripheral blood of children in the CHD and CHD-PAH groups were significantly lower ( P < 0.05 ) when compared to the control group. The expression levels of miR-204 and miR-451 in the peripheral blood of children in the CHD-PAH group were substantially lower ( P < 0.05 ) than in the CHD group. Significantly, the findings of the ROC curve revealed that the area under the curve (AUC) of CHD-PAH diagnosed by miR-204 and miR-451 alone was 0.737 and 0.725, respectively, and the AUC of joint diagnosis was 0.840, which was greater than that of single diagnosis ( P < 0.05 ). Patients with CHD-PAH had lower levels of miR-204 and miR-451 in their blood, and this was found to be associated with BNP, ADMA, and mPAP, analyzed by Pearson correlation. Conclusions. Children with CHD-PAH can be diagnosed based on aberrant expressions of miR-204 and miR-451 in their peripheral blood serum. Moreover, CHD-PAH can be diagnosed if the combination of miR-204 and miR-451 is detected as a biomarker, which has a higher diagnostic value.
30
Rajthala, Saroj, Anjie Min, Himalaya Parajuli, Kala Chand Debnath, Borghild Ljøkjel, Kristin Marie Hoven, Arild Kvalheim, et al. "Profiling and Functional Analysis of microRNA Deregulation in Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma Depicts an Anti-Invasive Role of microRNA-204 via Regulation of Their Motility." International Journal of Molecular Sciences 22, no. 21 (November 4, 2021): 11960. http://dx.doi.org/10.3390/ijms222111960.
Full textAbstract:
Background: Knowledge on the role of miR changes in tumor stroma for cancer progression is limited. This study aimed to investigate the role of miR dysregulation in cancer-associated fibroblasts (CAFs) in oral squamous cell carcinoma (OSCC). Methodology: CAF and normal oral fibroblasts (NOFs) were isolated from biopsies of OSCC patients and healthy individuals after informed consent and grown in 3D collagen gels. Total RNA was extracted. Global miR expression was profiled using Illumina version 2 panels. The functional impact of altered miR-204 expression in fibroblasts on their phenotype and molecular profile was investigated using mimics and inhibitors of miR-204. Further, the impact of miR-204 expression in fibroblasts on invasion of adjacent OSCC cells was assessed in 3D-organotypic co-cultures. Results: Unsupervised hierarchical clustering for global miR expression resulted in separate clusters for CAF and NOF. SAM analysis identified differential expression of twelve miRs between CAF and NOF. Modulation of miR-204 expression did not affect fibroblast cell proliferation, but resulted in changes in the motility phenotype, expression of various motility-related molecules, and invasion of the adjacent OSCC cells. 3′ UTR miR target reporter assay showed ITGA11 to be a direct target of miR-204. Conclusions: This study identifies differentially expressed miRs in stromal fibroblasts of OSCC lesions compared with normal oral mucosa and it reveals that one of the significantly downregulated miRs in CAF, miR-204, has a tumor-suppressive function through inhibition of fibroblast migration by modulating the expression of several different molecules in addition to directly targeting ITGA11.
31
Pulcrano, Salvatore, Roberto De Gregorio, Claudia De Sanctis, Laura Lahti, Carla Perrone-Capano, Donatella Ponti, Umberto di Porzio, et al. "Lmx1a-Dependent Activation of miR-204/211 Controls the Timing of Nurr1-Mediated Dopaminergic Differentiation." International Journal of Molecular Sciences 23, no. 13 (June 23, 2022): 6961. http://dx.doi.org/10.3390/ijms23136961.
Full textAbstract:
The development of midbrain dopaminergic (DA) neurons requires a fine temporal and spatial regulation of a very specific gene expression program. Here, we report that during mouse brain development, the microRNA (miR-) 204/211 is present at a high level in a subset of DA precursors expressing the transcription factor Lmx1a, an early determinant for DA-commitment, but not in more mature neurons expressing Th or Pitx3. By combining different in vitro model systems of DA differentiation, we show that the levels of Lmx1a influence the expression of miR-204/211. Using published transcriptomic data, we found a significant enrichment of miR-204/211 target genes in midbrain dopaminergic neurons where Lmx1a was selectively deleted at embryonic stages. We further demonstrated that miR-204/211 controls the timing of the DA differentiation by directly downregulating the expression of Nurr1, a late DA differentiation master gene. Thus, our data indicate the Lmx1a-miR-204/211-Nurr1 axis as a key component in the cascade of events that ultimately lead to mature midbrain dopaminergic neurons differentiation and point to miR-204/211 as the molecular switch regulating the timing of Nurr1 expression.
32
Ma, Hongzhi, Qian Shi, Jugao Fang, Ru Wang, Jianyu Zhao, Sitong Lin, Jiajing Dong, et al. "Long non-coding RNA AFAP1-AS1 promotes thyroid cancer progression by sponging miR-204-3p and upregulating DUSP4." Journal of Biochemistry 171, no. 1 (October 15, 2021): 131–40. http://dx.doi.org/10.1093/jb/mvab109.
Full textAbstract:
Abstract Long non-coding RNA actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1) shows crucial regulatory function in tumor progression. Nonetheless, the biological function and underlying mechanism of AFAP1-AS1 in the progression of thyroid cancer is still unclear. Expressions of AFAP1-AS1, miR-204-3p and DUSP4 were quantified utilizing quantitative real-time polymerase chain reaction and/or western blot. In loss-of-function and gain-of-function assays, cell proliferation, migration and invasion were appraised by CCK-8 assay, wound healing assay, Transwell migration and invasion assays, respectively. Luciferase reporter assay was employed for validating the interaction between miR-204-3p and AFAP1-AS1 or the 3’UTR of dual specificity phosphatase 4 (DUSP4). AFAP1-AS1 was highly expressed in thyroid cancer tissues and cell lines. Highly expressed AFAP1-AS1 was in association with advanced TNM stage and positive lymph node metastasis. Knockdown of AFAP1-AS1 suppressed the proliferation, migration and invasion of thyroid cancer cells, and overexpression of AFAP1-AS1 induced a reversed effect. MiR-204-3p was targetedly repressed by AFAP1-AS1, and miR-204-3p could negatively regulate DUSP4 expression. AFAP1-AS1 augmented the expression of DUSP4 via repressing miR-204-3p, and the effects of AFAP1-AS1 overexpression on thyroid cancer cells were also partly abolished by miR-204-3p restoration. In summary, AFAP1-AS1 facilitates thyroid cancer cell proliferation, migration and invasion by regulating miR-204-3p/DUSP4 axis.
33
Lin, Yihui, and Jianjia Jiang. "Long non-coding RNA LINC00704 promotes cell proliferation, migration, and invasion in papillary thyroid carcinoma via miR-204-5p/HMGB1 axis." Open Life Sciences 15, no. 1 (August 12, 2020): 561–71. http://dx.doi.org/10.1515/biol-2020-0057.
Full textAbstract:
AbstractPapillary thyroid carcinoma (PTC) is a common malignancy worldwide. LncRNA LINC00704 (mitotically associated long non-coding RNA) was reported as a crucial regulator in PTC. However, the biological mechanism of LINC00704 action remains unclear in PTC. The mRNA levels of LINC00704, miR-204-5p, and high-mobility group box 1 (HMGB1) were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay. HMGB1, proliferating cell nuclear antigen (PCNA), and cyclin D1 protein levels were detected using the Western blot assay. The binding relationship between miR-204-5p and LINC00704 or HMGB1 was predicted by LncBase Predicted v.2 or TargetScan, respectively, and then validated by dual luciferase reporter assay. Cell viability, cell cycle, cell migration and invasion, and migration ratio were assessed by MTT, flow cytometry, transwell cell migration and invasion, and wound-healing assays, respectively. Results suggested that LINC00704 and HMGB1 were elevated and miR-204-5p decreased in PTC tissues and cells. Furthermore, rescue experiments demonstrated that the miR-204-5p inhibitor alleviated the inhibitory effects of LINC00704 knockdown on cell proliferation, cell cycle, migration, and invasion. Meanwhile, miR-204-5p overexpression repressed proliferation, migration, and invasion by targeting HMGB1. Mechanical analysis discovered that LINC00704 could act as an miR-204-5p sponge to modulate HMGB1 expression. In conclusion, LINC00704 promoted PTC cell proliferation, cell cycle, migration, and invasion by the miR-204-5p/HMGB1 axis, providing a novel therapeutic target for PTC patients.
34
Lin, Zheng, Hui Wang, Junyou Wang, Gaojun Lin, and Da Lin. "Effects of LncRNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) Regulating Bcl-2 on Glioma Cell Proliferation and Apoptosis Through Regulating MiR-204 Expression." Journal of Biomaterials and Tissue Engineering 10, no. 2 (February 1, 2020): 234–38. http://dx.doi.org/10.1166/jbt.2020.2245.
Full textAbstract:
Objective: To investigate lncRNA MALAT1’s effect on glioma cell proliferation and apoptosis. Methods: qRT-PCR was applied to detect the MALAT1 RNA expression in para-carcinoma and carcinoma tissues of patients with brain glioma. After MALAT1 knockdown with small interfering RNA (siRNA) in U87 cell line, MALAT1 and miR-204 expression levels were measured by qRT-PCR and cell proliferation was measured by CCK-8 assay. The U87 cell line with overexpressed miR-204 expression was constructed and miR-204 expression was detected by qRT-PCR. The CCK-8 assay and flow cytometer were adopted to determine cell proliferation and apoptosis, respectively. Annexin V/propidium iodide (AV/PI) staining was conducted to detect cell apoptosis. Targets can target gene prediction website predicted the target of miR-204 and Bcl-2 level was detected by qRT-PCR and Western blot. Results: MALAT1 RNA in glioma tissues was significantly upregulated compared to para-carcinoma tissues (p < 0.05). After MALAT1 RNA expression was down-regulated by trans-fecting of MALAT1 siRNA, miR-204 expression was elevated, while cell viability was reduced. Moreover, overexpression of miR-204 significantly decreased Bcl-2 mRNA and protein level (p < 0.05), reduced cell viability (p < 0.05), and increased cell apoptosis rate (p < 0.05). Conclusion: miR-204 can be up-regulated by suppressing lncRNA MALAT1 expression, thus controlling Bcl-2 expression, resulting in inhibition of proliferation of glioma cells and promotion of cell apoptosis.
35
Kang, Donghyun, Jungkwon Shin, Yongsik Cho, Hyeon-Seop Kim, Young-Ran Gu, Haedong Kim, Kwon Tae You, et al. "Stress-activated miR-204 governs senescent phenotypes of chondrocytes to promote osteoarthritis development." Science Translational Medicine 11, no. 486 (April 3, 2019): eaar6659. http://dx.doi.org/10.1126/scitranslmed.aar6659.
Full textAbstract:
A progressive loss of cartilage matrix leads to the development of osteoarthritis (OA). Matrix homeostasis is disturbed in OA cartilage as the result of reduced production of cartilage-specific matrix and increased secretion of catabolic mediators by chondrocytes. Chondrocyte senescence is a crucial cellular event contributing to such imbalance in matrix metabolism during OA development. Here, we identify miR-204 as a markedly up-regulated microRNA in OA cartilage. miR-204 is induced by transcription factors GATA4 and NF-κB in response to senescence signals. Up-regulated miR-204 simultaneously targets multiple components of the sulfated proteoglycan (PG) biosynthesis pathway, effectively shutting down PG anabolism. Ectopic expression of miR-204 in joints triggers spontaneous cartilage loss and OA development, whereas miR-204 inhibition ameliorates experimental OA, with concomitant recovery of PG synthesis and suppression of inflammatory senescence-associated secretory phenotype (SASP) factors in cartilage. Collectively, we unravel a stress-activated senescence pathway that underlies disrupted matrix homeostasis in OA cartilage.
36
Medina, Kay, Zhiuhu Xu, and Kimberly Gwin. "The role of miR-204 in early B cell development. (HEM1P.219)." Journal of Immunology 194, no. 1_Supplement (May 1, 2015): 50.2. http://dx.doi.org/10.4049/jimmunol.194.supp.50.2.
Full textAbstract:
Abstract The generation of B lineage lymphocytes in bone marrow is contingent upon the combinatorial activities of transcription factors, signaling molecules, chromatin modifiers, and microRNAs. One transcription factor important for the generation of B cell precursors is the homeodomain protein HoxA9. Equally important as HoxA9 function in facilitating lymphoid lineage specification is silencing HoxA9 activity upon commitment to the B cell fate as sustained expression impairs later stage B cell differentiation. We previously showed that transcripts for the B cell specification factor EBF1 show an inverse expression pattern to HoxA9. Furthermore, EBF1 does not directly suppress HoxA9 transcription. Hox proteins are regulated by microRNAs in some developmental contexts. MicroRNA profiling of an EBF1-/- cell line stably expressing an inducible EBF1:ER fusion protein revealed a single miR induced by EBF1 activity, miR-204. Importantly, forced expression of miR-204 in EBF1-/- cells repressed transcription and protein levels of the HoxA9 co-factor, Meis1. We hypothesized that if Meis1 is a critical target of miR-204, then sustained expression of miR-204 should phenocopy conditional deletion of Meis1 or HoxA9. Indeed, we determined that forced expression of miR-204 in wildtype multipotent progenitors impaired B cell differentiation, similar to loss of HoxA9. These data suggest a novel role for EBF1 in B cell development, induction of miR-204 to silence a HoxA9-Meis1 transcriptional axis.
37
Koyama, Riko, Tiphaine Mannic, Jumpei Ito, Laurence Amar, Maria-Christina Zennaro, Michel Rossier, and Andrés Maturana. "MicroRNA-204 Is Necessary for Aldosterone-Stimulated T-Type Calcium Channel Expression in Cardiomyocytes." International Journal of Molecular Sciences 19, no. 10 (September 27, 2018): 2941. http://dx.doi.org/10.3390/ijms19102941.
Full textAbstract:
Activation of the mineralocorticoid receptor (MR) in the heart is considered to be a cardiovascular risk factor. MR activation leads to heart hypertrophy and arrhythmia. In ventricular cardiomyocytes, aldosterone induces a profound remodeling of ion channel expression, in particular, an increase in the expression and activity of T-type voltage-gated calcium channels (T-channels). The molecular mechanisms immediately downstream from MR activation, which lead to the increased expression of T-channels and, consecutively, to an acceleration of spontaneous cell contractions in vitro, remain poorly investigated. Here, we investigated the putative role of a specific microRNA in linking MR activation to the regulation of T-channel expression and cardiomyocyte beating frequency. A screening assay identified microRNA 204 (miR-204) as one of the major upregulated microRNAs after aldosterone stimulation of isolated neonatal rat cardiomyocytes. Aldosterone significantly increased the level of miR-204, an effect blocked by the MR antagonist spironolactone. When miR-204 was overexpressed in isolated cardiomyocytes, their spontaneous beating frequency was significantly increased after 24 h, like upon aldosterone stimulation, and messenger RNAs coding T-channels (CaV3.1 and CaV3.2) were increased. Concomitantly, T-type calcium currents were significantly increased upon miR-204 overexpression. Specifically repressing the expression of miR-204 abolished the aldosterone-induced increase of CaV3.1 and CaV3.2 mRNAs, as well as T-type calcium currents. Finally, aldosterone and miR-204 overexpression were found to reduce REST-NRSF, a known transcriptional repressor of CaV3.2 T-type calcium channels. Our study thus strongly suggests that miR-204 expression stimulated by aldosterone promotes the expression of T-channels in isolated rat ventricular cardiomyocytes, and therefore, increases the frequency of the cell spontaneous contractions, presumably through the inhibition of REST-NRSF protein.
38
Ding, Yao-dong, Yu-qiang Pei, Rui-Wang, Jia-xin Yang, Ying-xin Zhao, Xiao-li Liu, Hua Shen, Qian Ma, Shuo Zhang, and Hai-long Ge. "Association of Plasma MiRNA-204 and the Presence and Severity of Coronary Artery Calcification in Patients With Type 2 Diabetes." Angiology 72, no. 5 (January 5, 2021): 451–58. http://dx.doi.org/10.1177/0003319720984592.
Full textAbstract:
We investigated the association between plasma microRNA (miR)-204 and coronary artery calcification (CAC) in patients with type 2 diabetes mellitus (T2DM). We consecutively enrolled 179 individuals with T2DM who underwent coronary computed tomography at Anzhen Hospital from January 2015 to September 2016. The CAC score (CACS) was expressed in Agatston units and >10 Hounsfield units were defined as CAC-positive status. Significant CAC was observed in 98 (54.7%) patients. Plasma miR-204 levels (relative expression) were significantly lower in patients with significant CAC than controls (1.001 ± 0.100 vs 0.634 ± 0.211, P < .001). Plasma miR-204 levels were also negatively correlated with the glycosylated hemoglobin A1c (HbA1c) level (r = −0.702, P < .001), CACS (r = −0.710, P < .001), and the United Kingdom Prospective Diabetes Study (UKPDS) score (r = −0.355, P < .001). After multivariate logistic analyses, plasma miR-204 levels were still significantly and independently associated with the presence of CAC (odds ratio = 0.103, CI = 0.018-0.583, P < .001) after adjustment for conventional risk factors. Receiver operating characteristic curve analysis showed that plasma miR-204 levels can predict the severity and extent of CAC, and the specificity was higher than that of the traditional risk factors UKPDS score and HbA1c. In conclusion, the downregulation of miR-204 was independently associated with CAC in patients with T2DM.
39
Bereimipour, Ahmad, Leila Satarian, and Sara Taleahmad. "Investigation of Key Signaling Pathways Associating miR-204 and Common Retinopathies." BioMed Research International 2021 (October 4, 2021): 1–13. http://dx.doi.org/10.1155/2021/5568113.
Full textAbstract:
MicroRNAs are a large group of small noncoding RNAs that work in multiple cellular pathways. miR-204, as one of the key axes in the development, maintenance, and pathogenesis of the retina, plays several roles by modulating its target genes. This study was aimed at evaluating the target genes of miR-204 involved in the development and progression of common retinopathies such as glaucoma, retinoblastoma, and age-related macular degeneration. In this study, three datasets related to retinopathies (GSE50195, GSE27276, and GSE97508) were selected from Gene Expression Omnibus. miR-204 target genes were isolated from TargeScan. The shares between retinopathy and miR-204 target genes were then categorized. Using Enrichr and STRING, we highlighted the signaling pathways and the relationships between the proteins. SHC1 events in ERBB2, adherent junction’s interactions, NGF signaling via TRKA from the plasma membrane, IRF3-mediated activation of type 1 IFN, pathways in upregulated genes and G0 and early G1, RORA-activated gene expression, PERK-regulated gene expression, adherent junction’s interactions, and CREB phosphorylation pathways in downregulated genes were identified in glaucoma, retinoblastoma, and age-related macular degeneration. WEE1, SMC2, HMGB1, RRM2, and POLA1 proteins were also observed to be involved in the progression and invasion of retinoblastoma; SLC24A2 and DTX4 in age-related macular degeneration; and EPHB6, EFNB3, and SHC1 in glaucoma. Continuous bioinformatics analysis has shown that miR-204 has a significant presence and expression in retinal tissue, and approximately 293 genes are controlled and regulated by miR-204 in this tissue; also, target genes of miR-204 have the potential to develop various retinopathies; thus, a study of related target genes can provide appropriate treatment strategies in the future.
40
Yu, Xiaobo, Qiang Lin, Fabing Liu, Fu Yang, Jingyu Mao, and Xi Chen. "LncRNA TMPO-AS1 facilitates the proliferation and metastasis of NSCLC cells by up-regulating ERBB2 via sponging miR-204-3p." International Journal of Immunopathology and Pharmacology 34 (January 2020): 205873842095894. http://dx.doi.org/10.1177/2058738420958947.
Full textAbstract:
Introduction: This study aims at probing into the expression and biological function of long non-coding RNA (lncRNA) TMPO-AS1 in non-small cell lung cancer (NSCLC), and exploring its regulatory role for miR-204-3p and erb-b2 receptor tyrosine kinase 2 (ERBB2). Methods: In this study, paired NSCLC samples were collected, and the expression levels of TMPO-AS1, miR-204-3p and ERBB2 were examined by quantitative real-time polymerase chain reaction (qRT-PCR); proliferative ability and colony formation ability were detected by CCK-8 assay and plate colony formation assay, respectively; flow cytometry was performed to detect the effect of TMPO-AS1 on apoptosis; Transwell assay was used to detect the changes of migration and invasion; qRT-PCR and Western blot were utilised to analyse the changes of miR-204-3p and ERBB2 regulated by TMPO-AS1; luciferase reporter gene assay and RNA immunoprecipitation assay were employed to determine the regulatory relationship between TMPO-AS1 and miR-204-3p. Results: We demonstrated that TMPO-AS1 was significantly up-regulated in cancerous tissues of NSCLC samples, and positively correlated with the expression of ERBB2, while negatively correlated with miR-204-3p. After transfection of TMPO-AS1 shRNAs into NSCLC cells, the malignant phenotypes of NSCLC cells were significantly inhibited, while overexpression of TMPO-AS1 had opposite effects; TMPO-AS1 was also demonstrated to regulate the expression of miR-204-3p by sponging it, and indirectly modulate the expression of ERBB2. Conclusion: Collectively, we conclude that TMPO-AS1 has the potential to be the ‘ceRNA’ to regulate the expression of ERBB2 by sponging miR-204-3p in NSCLC.
41
Wu, Long-Fei, Qin Zhang, Xing-Bo Mo, Jun Lin, Yang-Lin Wu, Xin Lu, Pei He, et al. "Identification of novel rheumatoid arthritis-associated MiRNA-204-5p from plasma exosomes." Experimental & Molecular Medicine 54, no. 3 (March 2022): 334–45. http://dx.doi.org/10.1038/s12276-022-00751-x.
Full textAbstract:
AbstractRheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of immune cells in the synovium. However, the crosstalk of immune cells and synovial fibroblasts is still largely unknown. Here, global miRNA screening in plasma exosomes was carried out with a custom microarray (RA patients vs. healthy controls = 9:9). A total of 14 exosomal miRNAs were abnormally expressed in the RA patients. Then, downregulated expression of exosomal miR-204-5p was confirmed in both the replication (RA patients vs. healthy controls = 30:30) and validation groups (RA patients vs. healthy controls = 56:60). Similar to the findings obtained in humans, a decreased abundance of exosomal miR-204-5p was observed in mice with collagen-induced arthritis (CIA). Furthermore, Spearman correlation analysis indicated that plasma exosomal miR-204-5p expression was inversely correlated with disease parameters of RA patients, such as rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein. In vitro, our data showed that human T lymphocytes released exosomes containing large amounts of miR-204-5p, which can be transferred into synovial fibroblasts, inhibiting cell proliferation. Overexpression of miR-204-5p in synovial fibroblasts suppressed synovial fibroblast activation by targeting genes related to cell proliferation and invasion. In vivo assays found that administration of lentiviruses expressing miR-204-5p markedly alleviated the disease progression of the mice with CIA. Collectively, this study identified a novel RA-associated plasma exosomal miRNA-204-5p that mediates the communication between immune cells and synovial fibroblasts and can be used as a potential biomarker for RA diagnosis and treatment.
42
Li, Hua, Jibo Wang, Xiaoru Liu, and Qiang Cheng. "MicroRNA-204-5p suppresses IL6-mediated inflammatory response and chemokine generation in HK-2 renal tubular epithelial cells by targeting IL6R." Biochemistry and Cell Biology 97, no. 2 (April 2019): 109–17. http://dx.doi.org/10.1139/bcb-2018-0141.
Full textAbstract:
During the pathogenetic process of varied kidney diseases, renal tubules are the major sites in response to detrimental insults, including pro-inflammatory stimuli. MicroRNA-204-5p (miR-204-5p) can be detected in the renal tubular epithelial cells in the normal kidney; its expression, however, is downregulated in the kidney with pathological changes. This study aimed to investigate the role of miR-204-5p in interleukin 6 (IL6) mediated inflammatory response and chemokine production in HK-2 renal tubular cells. In HK-2 cells, the expression of miR-204-5p was downregulated in response to exogenous pro-inflammatory stimulus, tumor necrosis factor α (TNFα), or IL1β, while that of IL6 receptor α (IL6R) was upregulated. Dual-luciferase results confirmed that miRNA-204-5p directly targeted IL6R. In addition to suppressing IL6R expression, miRNA-204-5p agomir also inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in HK-2 cells exposed to exogenous IL6. Further, miRNA-204-5p suppressed the overproduction of pro-inflammatory mediators (cyclooxygenase 2 and prostaglandin E2) and chemokines (C–C motif chemokine ligand 2 and C–X–C motif chemokine ligand 8). The anti-inflammatory effects of miRNA-204-5p were attenuated when IL6R was reexpressed in HK-2 cells. Collectively, our study reveals that miR-204-5p inhibits the inflammation and chemokine generation in renal tubular epithelial cells by modulating the IL6/IL6R axis.
43
Tan, Yi Jayne, Benjamin Y. X. Wong, Ramanathan Vaidyanathan, Sivaramapanicker Sreejith, Sook Yoong Chia, Nagaendran Kandiah, Adeline S. L. Ng, and Li Zeng. "Altered Cerebrospinal Fluid Exosomal microRNA Levels in Young-Onset Alzheimer’s Disease and Frontotemporal Dementia." Journal of Alzheimer's Disease Reports 5, no. 1 (October 28, 2021): 805–13. http://dx.doi.org/10.3233/adr-210311.
Full textAbstract:
Background: micro-RNAs (miRNAs) are stable, small, non-coding RNAs enriched in exosomes. Their variation in levels according to different disease etiologies have made them a promising diagnostic biomarker for neurodegenerative diseases such as Alzheimer’s disease (AD). Altered expression of miR-320a, miR-328-3p, and miR-204-5p have been reported in AD and frontotemporal dementia (FTD). Objective: To determine their reliability, we aimed to examine the expression of three exosomal miRNAs isolated from cerebrospinal fluid (CSF) of patients with young-onset AD and FTD (< 65 years), correlating with core AD biomarkers and cognitive scores. Methods: Exosomes were first isolated from CSF samples of 48 subjects (8 controls, 28 AD, and 12 FTD), followed by RNA extraction and quantitative PCR to measure the expression of miR-320a, miR-328-3p, and miR-204-5p. Results: Expression of all three markers (miR-320a (p = 0.005), miR-328-3p (p = 0.049), and miR-204-5p (p = 0.036)) were significantly lower in AD versus controls. miR-320a was reduced in FTD versus controls (p = 0.049) and miR-328-3p was lower in AD versus FTD (p = 0.054). Notably, lower miR-328-3p levels could differentiate AD from FTD and controls with an AUC of 0.702, 95% CI: 0.534– 0.870, and showed significant correlation with lower CSF Aβ42 levels (r = 0.359, p = 0.029). Pathway enrichment analysis identified potential targets of miR-328-3p implicated in the AMPK signaling pathway linked to amyloid-β and tau metabolism in AD. Conclusion: Overall, we demonstrated miR-320a and miR-204-5p as reliable biomarkers for AD and FTD and report miR-328-3p as a novel AD biomarker.
44
Todorova, Krassimira, Diana Zasheva, Kristiyan Kanev, and Soren Hayrabedyan. "miR-204 Shifts the Epithelial to Mesenchymal Transition in Concert with the Transcription Factors RUNX2, ETS1, and cMYB in Prostate Cancer Cell Line Model." Journal of Cancer Research 2014 (October 14, 2014): 1–14. http://dx.doi.org/10.1155/2014/840906.
Full textAbstract:
Epithelial to mesenchymal transition is an essential step in advanced cancer development. Many master transcription factors shift their expression to drive this process, while noncoding RNAs families like miR-200 are found to restrict it. In this study we investigated how the tumor suppressor miR-204 and several transcription factors modulate main markers of mesenchymal transformation like E- and N-cadherin, SLUG, VEGF, and SOX-9 in prostate cancer cell line model (LNCaP, PC3, VCaP, and NCI-H660). We found that SLUG, E-cadherin, and N-cadherin are differentially modulated by miR-204, using miR-204 specific mimics and inhibitors and siRNA gene silencing (RUNX2, ETS-1, and cMYB). The genome perturbation associated TMPRSS2-ERG fusion coincided with shift from tumor-suppressor to tumor-promoting activity of this miRNA. The ability of miR-204 to suppress cancer cell viability and migration was lost in the fusion harboring cell lines. We found differential E-cadherin splicing corroborating to miR-204 modulatory effects. RUNX2, ETS1, and cMYB are involved in the regulation of E-cadherin, N-cadherin, and VEGFA expression. RUNX2 knockdown results in SOX9 downregulation, while ETS1 and cMYB silencing result in SOX9 upregulation in VCaP cells. Their expression was found to be also methylation dependent. Our study provides means for understanding cancer heterogeneity in regard to adapted therapeutic approaches development.
45
Han, Xu, Qiaobei Li, Chunyan Wang, and Yinyan Li. "MicroRNA-204-3p Attenuates High Glucose-Induced MPC5 Podocytes Apoptosis by Targeting Braykinin B2 Receptor." Experimental and Clinical Endocrinology & Diabetes 127, no. 06 (June 25, 2018): 387–95. http://dx.doi.org/10.1055/a-0630-0173.
Full textAbstract:
Abstract Background Previous study has been reported that braykinin B2 receptor (Bdkrb2) involves in high glucose-induced renal and podocytes injuries. However, there have been some studies with contradictory results that Bdkrb2 has a protective effect on hyperglycemia-induced injuries in vivo and in vitro. The purpose of the present study was carried out to further investigate the post-transcriptional regulatory mechanism of microRNA (miR) in high glucose-treated podocytes by targeting Bdkrb2 signaling in vitro. Methods The CCK-8 and flow cytometry were performed to measure the cell viability and apoptosis. Gene and protein expression were assayed by RT-qPCR and western blotting, respectively. Results High glucose treatment decreased cell viability and induced membrane and DNA damage, as well as apoptosis in podocytes. High glucose treatment also increased the expression of Bdkrb2, which was blocked by miR-204-3p mimics transfection in podocytes. Bioinformatics and luciferase reporter activity showed that miR-204-3p was directly targeted to the 3′-untranslated region (3′-UTR) of Bdkrb2. High glucose-induced apoptosis and dysfunction in podocytes were reserved by miR-204-3p mimics transfection, while the effects of miR-204-3p mimics in high glucose-treated podocytes were neutralized by overexpressed Bdkrb2. Conclusions These findings suggested that miR-204-3p may play a protective role in high glucose-induced apoptosis and dysfunction in podocytes through down-regulation of Bdkrb2.
46
Son, Ju Cheol, Hyoung Oh Jeong, Deaui Park, Sang Gyoon No, Eun Kyeong Lee, Jaewon Lee, and Hae Young Chung. "miR-10a and miR-204 as a Potential Prognostic Indicator in Low-Grade Gliomas." Cancer Informatics 16 (January 1, 2017): 117693511770287. http://dx.doi.org/10.1177/1176935117702878.
Full textAbstract:
This study aimed to identify and characterize microRNAs (miRNAs) that are related to radiosensitivity in low-grade gliomas (LGGs). The miRNA expression levels in radiosensitive and radioresistant LGGs were compared using The Cancer Genome Atlas database, and differentially expressed miRNAs were identified using the EBSeq package. The miRNA target genes were predicted using Web databases. Fifteen miRNAs were differentially expressed between the groups, with miR-10a and miR-204 being related to overall survival (OS) of patients with LGG. Patients with upregulated miR-10a expression had a higher mortality rate and shorter OS time, whereas patients with downregulated miR-204 expression had a lower mortality rate and longer OS time. Two genes, HSP90AA1 and CREB5, were targets for both miRNAs. Thus, this study suggests that expression of miR-10a and miR-204 is significantly related to both radiosensitivity and the survival of patients with LGG. These miRNAs could therefore act as clinical biomarkers for LGG prognosis and diagnosis.
47
Zhuo, Jiuwu, Yishan Zheng, Wanying Hu, and Guoping Yin. "Sufentanil Inhibits Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells by Upregulating miRNA-204." Journal of Biomaterials and Tissue Engineering 11, no. 4 (April 1, 2021): 718–24. http://dx.doi.org/10.1166/jbt.2021.2561.
Full textAbstract:
Sufentanil is a powerful analgesic that acts on μ-receptors, but there are few studies on sufentanil in cancer. The biological function and underlying mechanisms of sufentanil on the hepatocellular carcinoma (HCC) cells were explored in the present study. HCC cells were first treated with different concentrations of sufentanil and the most optimum concentration of sufentanil was determined. The expression of miR-204 in HCC cells was changed by transfected with miR-204 inhibitor and the transfection efficiency was assessed by qRT-PCR. CCK-8, wound-healing and Transwell assays were performed to evaluate the proliferation, migration and invasion of HCC cells, respectively. The level of AKT and PI3K phosphorylation (p-AKT and p-PI3K) were assessed by western blot analysis. Our results demonstrated that sufentanil effectively inhibited cell proliferation,migration and invasion in both Huh7 and Hep3B cells, and significantly decreased the expression of p-AKT and p-PI3K. In addition, miR-204 was upregulated in Huh7 and Hep3B cells treated with sufentanil, and low expression of miR-204 attenuated the damage of sufentanil on the viability of Huh7 and Hep3B cells. Taken together, sufentanil suppressed the proliferation, migration and invasion of HCC cells via inhibiting AKT/PI3K signaling pathway by targeting miR-204.
48
Khalid, Muhammad, Tetsuya Idichi, Naohiko Seki, Masumi Wada, Yasutaka Yamada, Haruhi Fukuhisa, Hiroko Toda, et al. "Gene Regulation by Antitumor miR-204-5p in Pancreatic Ductal Adenocarcinoma: The Clinical Significance of Direct RACGAP1 Regulation." Cancers 11, no. 3 (March 7, 2019): 327. http://dx.doi.org/10.3390/cancers11030327.
Full textAbstract:
Previously, we established a microRNA (miRNA) expression signature in pancreatic ductal adenocarcinoma (PDAC) tissues using RNA sequencing and found significantly reduced expression of miR-204-5p. Here, we aimed to investigate the functional significance of miR-204-5p and to identify miR-204-5p target genes involved in PDAC pathogenesis. Cancer cell migration and invasion were significantly inhibited by ectopic expression of miR-204-5p in PDAC cells. Comprehensive gene expression analyses and in silico database searches revealed 25 putative targets regulated by miR-204-5p in PDAC cells. Among these target genes, high expression levels of RACGAP1, DHRS9, AP1S3, FOXC1, PRP11, RHBDL2 and MUC4 were significant predictors of a poor prognosis of patients with PDAC. In this study, we focused on RACGAP1 (Rac guanosine triphosphatase-activating protein 1) because its expression was most significantly predictive of PDAC pathogenesis (overall survival rate: p = 0.0000548; disease-free survival rate: p = 0.0014). Overexpression of RACGAP1 was detected in PDAC clinical specimens, and its expression enhanced the migration and invasion of PDAC cells. Moreover, downstream genes affected by RACGAP1 (e.g., MMP28, CEP55, CDK1, ANLN and S100A14) are involved in PDAC pathogenesis. Our strategy to identify antitumor miRNAs and their target genes will help elucidate the molecular pathogenesis of PDAC.
49
Lavrentiev, S. N., M. B. Aksenenko, A. S. Averchuk, A. V. Komina, N. V. Palkina, and T. G. Ruksha. "INCREASED LEVEL OF MIR-204-5P EXPRESSION IN MELANOMA CELLS UNDER THE INFLUENCE OF DACARBAZINE." Siberian journal of oncology 18, no. 3 (June 30, 2019): 45–53. http://dx.doi.org/10.21294/1814-4861-2019-18-3-45-53.
Full textAbstract:
Various types of tissues was analyzed, and the algorithm for summing neutron and photon doses in neutronMiRNA s are involved in the regulation of numerous critical biological processes, including cell proliferation, differentiation, migration and invasion. They function as oncogenes or tumor suppressors according to the nature of the target. It has been previously determined that miR-204-5p miRNA is characterized by the increased level in melanoma. The aim of this study was to determine the effects of changes in the level of microRNA expression when dacarbazine was exposed to melanoma cells in vitro and synthetic miR-204-5p in vivo. The expression levels of miR-204-5p and miR-211 in melanoma cells were determined by real-time PCR. Antitumor effects in vivo were verified in assessing the growth dynamics of the tumor node. Toxic effects were assessed by animal behavior, fluid intake, feed, and ALT , AST , creatinine, urea levels. In the model of melanoma C57BL6, it was revealed that the introduction of the synthetic miR-204-5p did not cause significant changes in the investigated microRNA in tumor cells. At the same time, the antitumor effects of dacarbazine in melanoma cells in vitro led to an increase in the level of the investigated microRNA by more than 20 times. The results of the study indicated the possibility of compensating the level of miR-204-5p under the influence of cytostatic therapy. Taking into account the previously revealed miR-204-5p inhibitory effect on the proliferation of melanoma cells, we can assume that this miRNA can play a role in maintaining the dermal state of tumor cells. Further studies are required to understand the metastasis development and predict the response to antitumor therapy for melanoma.
50
Jiang, Daqing, Xianxin Xie, Cong Wang, Weijie Li, and Jianjun He. "Exosomal MicroRNA-204 Derived from Bone Marrow Mesenchymal Stem Cells (BMSCs) Inhibits Cell Proliferation and Induces Apoptosis Through NF-κB Signaling Pathway in Breast Cancer." Journal of Biomaterials and Tissue Engineering 12, no. 2 (February 1, 2022): 273–78. http://dx.doi.org/10.1166/jbt.2022.2900.
Full textAbstract:
Our study intends to assess the relationship between exosomes derived from bone marrow mesenchymal stem cells (BMSC-exo) and breast cancer. BMSC-exo were isolated and characterized by transmission electron microscopy. After transfection of BMSCs with miR-204 inhibitor, breast cancer cells were incubated with BMSC-exo followed by analysis of cell proliferation by CCK-8 assay, cell apoptosis by flow cytometry, and expression of apoptosis-related protein and NF-κB signaling by western blot. The co-culture of BMSC-exo with breast cancer cells enhanced miR-204 transcription, inhibited cell proliferation and induced apoptosis. Further, BMSC-exo accelerated apoptosis as demonstrated by the increased level of Bax and casepase-3 and decreased Bcl-2 expression, as well as reduced NF-κB signaling activity. But knockdown of miR-204 abolished the effect of BMSC-exo on apoptosis and proliferation with NF-κB signaling activation. In conclusion, miR-204 from BMSC-exo restrains growth of breast cancer cell and might be a novel target for treating breast cancer.