Academic literature on the topic 'MiR-183-5p'

Background: MiR-183-5p plays an important role in the pathophysiology of many tumors, while the role of MiR-183-5p in liver cancer is unclear. Methods: In this study, quantitative reverse transcription-polymerase chain reaction and Western blotting were used to detect the expression of miR-183-5p in liver cancer cell lines, liver cancer tissues, and normal tissues adjacent to the cancer, and to explore the mechanism of miR-183-5p regulating liver cancer progression. The in vitro effects of miR-183-5p were evaluated by CCK-8, colony formation test, and wound healing test. Various databases were used to predict the target mRNA of miR-183-5p and verified by luciferase report analysis. In addition, the effects of miR-183-5p and its target gene on the survival of patients with liver cancer were also analyzed. Results: miR-183-5p was highly expressed in hepatocellular carcinoma cells and tissues, and was related to some clinicopathological features. MiR-183-5p can promote the proliferation and migration of liver cancer cells. Using the bioinformatics database, we proved that miR-183-5p is related to the survival of liver cancer patients. Insulin receptor substrate 1 (IRS1) is a target of miR-183-5p, and luciferase analysis confirmed that miR-183-5p combines with the 3′-untranslated region (3′-UTR) of IRS1. Conclusion: The miR-183-5p/IRS1 axis may be a new target for liver cancer research.

This study mainly explores how miR-183-5p pertains to breast cancer (BC) development. Functional assays were employed to test impacts of miR-183-5p in this cancer. Targeting between RGS2 and miR-183-5p was examined with dual-luciferase assay, and how their interaction pertains to cancer progression was further unraveled. miR-183-5p level was noticeably high in cancer tissue/cells. Overexpressing miR-183-5p could remarkably deteriorate cancer progression. The regulatory gene RGS2 levels was markedly low in BC, and two genes we researched were negatively correlated. It was uncovered by rescue assay that miR-183-5p/RGS2 axis mediated tumor-relevant behaviors in BC. Altogether, miR-183-5p aggravates BC development via mediation of RGS2. miR-183-5p supplies a promising target for BC therapy.

Currently, the treatment for ovarian cancer (OC) is not satisfactory. The microRNAs may have an important function in tumor pathogenesis. miR-183-5p involves in several tumors. However, its effect on OC cells is unclear. The BMSCs could regulate the micro-environment of tumor and participate in tumor procession. In this study, effect of BMSCs with highly-expressed miR-183-5p on OC cells was assessed. The BMSCs with highly-expressed miR-183-5p was established and co-cultivated with OC cell line SKOV3 followed by measuring miR-183-5p level by PCR, STAT3 and ADAM9 expression by western blot. miR-183-5p level in OC cells was reduced and further decreased after co-culture with BMSCs along with enhance cell proliferation and upregulated STAT3 expression (P < 0.05). In addition, miR-183-5p level was increased in BMSCs with highly-expressed miR-183-5p and STAT3 expression was reduced along with restrained cell proliferation (P < 0.05). In conclusion, miR-183-5p in OC cells is downregulated and malignant biological behaviors of OC cells are restrained by BMSCs with highly-expressed miR-183-5p possibly through regulating the expression of STAT3.

Receptive endometrium is a prerequisite for successful embryo implantation, and it follows that poor endometrial receptivity is a leading cause of implantation failure. miRNAs play important roles as epigenetic regulators of endometrial receptivity and embryo implantation through post-transcriptional modifications. However, the mechanisms of action of many miRNAs are poorly understood. In this study, we investigated the role of the miR-183 family, comprising three miRNAs (miR-183-5p, miR-182-5p, and miR-96-5p) in endometrial receptivity and embryo implantation. The miR-183 family shows estrogen-dependent upregulation in endometrial Ishikawa (IK) cells. The miR-183 family also has a positive role in migration and proliferation of IK cells. Furthermore, JAr spheroid attachment experiments show that attachment rates were significantly decreased after treatment of IK cells with inhibitors for miR-183-5p and miR-182-5p and increased after treatment with miR-183-5p-mimic and miR-96-5p-mimic, respectively. The downstream analysis shows that catenin alpha 2 (CTNNA2) is a potential target gene for miR-183-5p, and this was confirmed in luciferase reporter assays. An in vivo mouse pregnancy model shows that inhibition of miR-183-5p significantly decreases embryo implantation rates and increases CTNNA2 expression. Downregulation of CTNNA2 in endometrial cells by miR-183-5p may be significant in mediating estrogenic effects on endometrial receptivity. In conclusion, miR-183-5p and the CTNNA2 gene may be potential biomarkers for endometrial receptivity and may be useful diagnostic and therapeutic targets for successful embryo implantation.

Abstract Backgrounds:Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by reduced platelet count and an increased risk of bleeding. The imbalance of Treg/Th17 cells has been demonstrated in ITP, but the mechanism of Th17/Treg cells imbalance is still not clear. In this study, we aimed to investigate whether the expression of helper T (Th) or Treg cell-related microRNAs, such as miR-183-96-182 cluster, miR-17-5p, miR-99a, miR-146-5p, miR-155-5p, miR-181-5p, and miR-326, regulates the ratio of Th17/Treg in CD4+ T cells and could be used to evaluate the clinical implications of ITP patients. Methods: Peripheral blood was obtained from 54 patients with active ITP and 34 healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll density-gradient centrifugation and the CD4+ cells were separated by immuno-magnetic microbeads selection. Amplification technique of RT-PCR using stem-loop primers was applied to detect the relative expression of microRNAs (miR-17-5p, miR-99a, miR-96-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, miR-182-5p, miR-183-5, miR-326) and U6 was normalized as control for miRNA quantification. The frequencies of Th17 and Treg cells in peripheral blood were analyzed by flow cytometry. The mRNA expression levels of Il-6, Il-10, Il-17, Rorγ-t and Foxp-3 in CD4+ cells were determined by RT-PCR. Platelet autoantibodies specific for GPIIb/IIIaor GPIb/IX were measured using MAIPA method. CD4+ cells were transfected with miRNAs (miR-99a, miR-182-5p, miR-183-5), mimics or inhibitors, which were used to detect the function of miRNAs. Cytokines in culture medium were determined by ELISA. Results: Our results showed that the relative expression of miR-182-5p and miR-183-5p in CD4+ cells was significantly increased in active ITP patients, compared to healthy controls (miR-182-5p, median 9.2678 vs 5.2723, p < 0.05, Fig. 1a; miR-183-5p, median 5.4435 vs 2.009, p < 0.05, Fig. 1b). In addition, the relative expression of miR-99a in ITP patients was lower than that of healthy controls (median 3.4214 vs 7.9648, p < 0.05; Fig. 1c). Moreover, the frequency of Treg cells decreased significantly in ITP patients compared to those in controls (1.89±1.59% vs 4.12±1.42%, p < 0.05; Fig. 2a), and the percentage of Treg cells was positively correlated with the relative expression of miR-99a in ITP patients(r=0.461, p< 0.05; Fig. 2c) and health controls(r=0.729, p< 0.05; Fig. 2d). Though the percentage of Th17 cells increased in ITP patients compared to the health controls (3.51±2.13%vs 1.85±0.63%, p < 0.05; Fig. 2b), there was no correlation between the percentage of Th17 and the relative expression of microRNAs in ITP patients or health controls. Besides, there was no correlation between the expression of mRNAs (Il-10, Il-17, Rorγ-t and Foxp-3) and microRNAs (miR-99a, miRNA-182-5p or miR-183-5p). No significant correlation was found between the microRNAs expression and platelets counts or different autoantibody subsets in ITP patients. The relative expression of other microRNAs (miR-17-5p, miR-96-5p, miR-146a-5p, miR-155-5p, miR-181-5p, miR-326) revealed no difference in CD4+ cells between ITP patients and health controls. Furthermore, the down-regulated expression of miR-183-5p with inhibitors promoted to the differentiation of Th17 cells(Fig. 3a), while up-regulated expression of miR-99a with mimics contributed to Treg cells in CD4+ cells from ITP patients (Fig. 3b). Meanwhile, the IL-17A in culture medium decreased in inhibitor group of miR-183-5p or miR-183-5p. However, miR-182-5p inhibitor had no effect on the differentiation of Th17 cells. Conclusions: Our results show the abnormal expression of microRNAs (miR-99a, miRNA-182-5p and miR-183-5p) in CD4+ cells and the miR-99a was closely correlated with the Treg cells. The aberrant expression of microRNAs may contribute to the imbalance of Th17/Treg cells in the development of ITP patients and potentially constitute a novel therapeutic target. Disclosures No relevant conflicts of interest to declare.

Neuroblastoma, a malignant tumor of the sympathetic nervous system, is an aggressive extracranial tumor in childhood. Long noncoding RNAs (lncRNAs) have been discovered to play a key role in the eukaryotic regulatory gene network and be involved in a wide variety of biological processes. We observed that the expression of lncRNA nuclear-enriched abundant transcript-1 (NEAT1) was significantly decreased in human neuroblastoma tissues and cell lines, compared with the normal. We observed cell proliferation, migration, and invasion with Cell Counting Kit-8 assay, colony formation assay, and Transwell assay to investigate the effects of NEAT1, miR-183-5p, or FOXP1 on neuroblastoma cells. And we also used StarBase and luciferase reporter gene assay to predict and confirm the interaction of NEAT1, miR-183-5p, and FOXP1 in neuroblastoma cells. First, overexpression of NEAT1 suppressed cell proliferation and played a key role in cell migration and invasion. In addition, NEAT1 was demonstrated to directly interact with miR-183-5p and exerted its antioncogenic role in neuroblastoma by negatively regulating miR-183-5p expression. miR-183-5p suppressed the expression of FOXP1 and regulated cell proliferation and migration by directly targeting FOXP1 mRNA 3′-untranslated region. Moreover, FOXP1 antagonized the effect of miR-183-5p on the phosphorylation of extracellular-regulated kinase/protein kinase B (ERK/AKT), while FOXP1 siRNA increased the reduced phosphorylation of ERK/AKT caused by miR-183-5p inhibitor in neuroblastoma cells. Taken together, these data showed that NEAT1 negatively regulated cell proliferation and migration of neuroblastoma by the miR-183-5p/FOXP1 axis via suppression of the ERK/AKT pathway. Our findings may provide a new target for the study of pathogenesis and treatment of neuroblastoma.

This study assessed P53′s role in BMSC osteogenic differentiation. Osteoporosis model was established and P53 expression in the osteogenic differentiation was detected by RT-PCR. BMSC was cultivated and transfected with siRNA followed by measuring presentation of osteogenic differentiation was detected after cells were. The apoptotic condition of osteogenic differentiation was detected through IF method and protein analysis. The relation between P53 and miR-153-5p/miR-183-5p-XIAP signal axis was detected through bioinformatics and luciferase reporter gene assay. P53 expression was significantly increased after osteogenic differentiation was induced. There was a binding site between P53 and miR-153-5p/miR-183-5p-XIAP signal axis. The apoptotic ability of osteoblast was enhanced after inhibition of the expression of P53. In conclusion, P53 develops crucial action on the regulation of BMSC osteogenic differentiation through miR-153-5p/miR-183-5p-XIAP axis.

Excessive saturated fatty acids (SFA) uptake is known to be a primary cause of obesity, a widely acknowledged risk factor of insulin resistance and type 2 diabetes. Although specific microRNAs (miRNAs) targeting insulin signaling intermediates are dysregulated by SFA, their effects on insulin signaling and sensitivity are largely unknown. Here, we investigated the role of SFA-induced miR-183-5p in the regulation of proximal insulin signaling molecules and the development of hepatic insulin resistance. HepG2 hepatocytes treated with palmitate and the livers of high-fat diet (HFD)-fed mice exhibited impaired insulin signaling resulting from dramatic reductions in the protein expressions of insulin receptor (INSR) and insulin receptor substrate-1 (IRS-1). Differential expression analysis showed the level of miR-183-5p, which tentatively targets the 3′UTR of IRS-1, was significantly elevated in palmitate-treated HepG2 hepatocytes and the livers of HFD-fed mice. Dual-luciferase analysis showed miR-183-5p bound directly to the 3′UTR of IRS-1 and reduced IRS-1 expression at the post-transcriptional stage. Moreover, transfection of HepG2 hepatocytes with miR-183-5p mimic significantly inhibited IRS-1 expression and hindered insulin signaling, consequently inhibiting insulin-stimulated glycogen synthesis. Collectively, this study reveals a novel mechanism whereby miR-183-5p induction by SFA impairs insulin signaling and suggests miR-183-5p plays a crucial role in the pathogenesis of hepatic insulin resistance in the background of obesity.

Curcumin (Cur), a natural polyphenol compound, has been testified to modulate innate immune responses and also showed anti-inflammatory properties. Nevertheless, the mechanism was still poorly unknown, especially regarding Cur-modulated microRNAs (miRNAs) under the inflammatory response. CD39+ regulatory T cells (Tregs) were provided with distinct immunosuppressive action and exerted a critical role in the modulation of immune balance in sepsis. Nevertheless, the impact of Cur on the immune function of sepsis mice has not been reported. In this study, the influence of Cur on the inflammatory response and immune function of sepsis mice via augment of miR-183-5p and Cathepsin B (CTSB)-mediated phosphatidylinositol 3-kinase (PI3K)/AKT pathway was explored. Adoption of 20 mg/kg Cur was for gavage. In the meantime, injection of plasmid vectors of interference with miR-183-5p or CTSB was into the tail vein. Intraperitoneal injection of lipopolysaccharide (10 mg/kg) was to stimulate model of sepsis mice. Histopathological changes of sepsis mice were observed. The contents of tumor necrosis factor-α and Interleukin (IL)-1β and IL-6 in serum of mice were examined. Detection of alanine aminotransferase, aspartate aminotransferase (AST), urea nitrogen (BUN), and creatinine in serum of mice was performed. Test of the percentage of CD39+ Tregs in tail venous blood of mice was implemented. Examination of miR-183-5p, CTSB, and PI3K/AKT was performed. The targeting of miR-183-5p and CTSB was detected. Cur was available to ameliorate the histological damage, to reduce the content of inflammatory factors, AST, and BUN, and to decline the percentage of CD39+ Tregs in tail venous blood of sepsis mice. Elevated miR-183-5p or silenced CTSB was available to further enhance the protection of Cur. Cur was available to accelerate miR-183-5p, which negatively modulated CTSB and Cur-mediated PI3K/AKT pathway via the miR-183-5p/CTSB axis to restrain inflammation of sepsis mice and enhance its immune function.

Purpose.This study aimed to determine the dynamic changes of NF-κB-related microRNAs (miRNAs) and cytokines over the course of experimental autoimmune anterior uveitis (EAAU) and elucidate the possible immunopathogenesis.Materials and Methods.Uveitis was induced in Lewis rats using bovine melanin-associated antigen. The inflammatory activity of the anterior chamber was clinically scored, and leukocytes in the aqueous humor were quantified. RNA was extracted from the iris/ciliary bodies and popliteal lymph nodes to reveal the dynamic changes of eight target miRNAs (miR-155-5p, miR-146a-5p, miR-182-5p, miR-183-5p, miR-147b, miR-21-5p, miR-9-3p, and miR-223-3p) and six cytokine mRNAs (IFN-γ, IL-17, IL-12A, IL-1β, IL-6, and IL-10).In situhybridization of miRNA and enzyme-linked immunosorbent assay quantification of cytokines were performed to confirm the results.Results. Disease activity and leukocyte quantification were maximum at day 15 after immunization. The profiling of miRNA revealed downregulation of miR-146a-5p, miR-155-5p, miR-223-3p, and miR-147b and upregulation of miR-182-5p, miR-183-5p, and miR-9-3p. Cytokine analysis revealed IFN-γ, IL-17, IL-12A, IL-1β, and IL-6 overexpression, with IL-10 downregulation.Conclusions.Dynamic changes of miRNAs were observed over the course of EAAU. By initiating NF-κB signaling, the expressions of downstream cytokines and effector cells from the Th17 and Th1 lineages were sequentially activated, contributing to the disease.

Type 1 diabetes (T1D) is a chronic multifactorial autoimmune disease that includes 5-10% of diabetes cases and is characterized by the immune-mediated insulin secreting β cell destruction with consequent loss of β cell mass and hyperglycemia. In autoimmune diabetes, the selective β cell destruction is the result of a series of mechanisms including, but not limiting to autoreactive T cells direct β cell destruction and inflammatory stress, resulting in a dramatic loss of functional β cell mass. MicroRNAs are small non coding 19-24 nucleotides RNAs that negatively regulate gene expression, binding selectively their mRNAs target and leading to their translational repression and/or degradation. It was also remarked that miRNAs are involved in T1D pathogenesis, by regulating a series of processes both in β cells and lymphocytes that ranged from cell metabolic dysfunction and apoptosis to dedifferentiation and immune molecule secretion. Additionally, it has been suggested that secreted microRNAs can take part in the communication between immune system and pancreatic endocrine cells; therefore, studying such dialogue could help to better understand T1D pathogenesis and to the identification of biomarkers that reflect the diseased status of the target organ. In order to investigate the role of miRNAs as biomarkers of T1D pathogenesis both at endocrine and immune interface, the study can be subdivided into the following sections: 1) MiRNAs as circulating biomarkers of diseased-target tissue- In this section, miR-409-3p was found downregulated in murine and human plasma of T1D subjects, highlight the importance to find a lymphocyte deriving circulating biomarker that reflect the target organ pathological status. 2) MiRNAs as modulators of β cell function- miR-183-5p was downregulated in pancreatic endocrine tissue of mouse and human diabetic patients, contributing to β cell protection from apoptosis through the modulation of anti-apoptotic factor Bach2 and through the potential induction of a dedifferentiation phenomenon. This study demonstrated that β cells are able to react to stress and to cell damage through a miRNA-mediated protective phenomenon. 3) Secreted/Immune-derived miRNAs as mediators of β cell apoptosis- Exosomes enriched in miR-142-3p/5p and miR-155 and secreted by T autoreactive lymphocytes, induced selective β cell apoptosis, through the modulation of proinflammatory chemokine expression. The selective AAV “Sponge” inactivation of miR-142-3p/5p, miR-150 and miR-155 induced β cell protection of prediabetic NOD mice from the autoimmune attack that occurs in T1D, inducing the reduction of the proinflammatory chemokine CXCL10 specifically in β cells than in α cells. Such study remarked the exosome-mediated communication dynamics between immune system components and endocrine cells in the center of this dialogue, miRNAs give their fundamental contribution and more importantly, as it has already been reported, it’s possible to actively and therapeutically interfere in this dialogue in order to positively change the β cell fate.