Щоб переглянути інші типи публікацій з цієї теми, перейдіть за посиланням: Cell-PCA.
Статті в журналах з теми "Cell-PCA"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-50 статей у журналах для дослідження на тему "Cell-PCA".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте статті в журналах для різних дисциплін та оформлюйте правильно вашу бібліографію.
1
HAGHIGHI-NAJAFABADI, NASRIN, SHIMA FAYAZ, GHAZAL HADDAD, MAHBOUBEH BERIZI, and PEZHMAN FARD-ESFAHANI. "MicroRNA 138 upregulation is associated with decreasing levels of CCND1 gene expression and promoting cell death in human prostate cancer cell lines." Romanian Biotechnological Letters 27, no. 6/2022 (April 23, 2023): 3768–78. http://dx.doi.org/10.25083/rbl/27.6/3768.3778.
Повний текст джерелаАнотація:
This research intended to discover the significance of miR-138 on the espression profile, proliferation, and the associated regulatory mechanisms in prostate cancer (PCa). RT-qPCR was applied to compare the expression of miR-138 in the PCa cells with a non-cancer cell line, as well as PCa tissue samples with benign prostatic hyperplasia (BPH) samples. The expression of miR-138 notably diminished in PCa tissues and cell lines. Afterward, formerly documented genes, along with bioinformatics analysis, suggested seven possible target genes of miR-138. Among them, CCND1 seemed to have higher expression in the PCa cell lines and tissues. Also, the negative correlation of miR-138 and CCND1 in PCa cell line and tissues was validated using Pearson correlation. CCDN1 was revealed to be the target gene of miR138 in the PC3 cell line based on the results of the luciferase reporter gene assay. Over-expression of miR138-5p suppressed the expression of CCDN1 in PCa cell lines as exhibited by RT-qPCR. Finally, the results of the MTT assay exhibited the inhibitory impact of miR-138 on the proliferative capacities in PCa cell lines. Our research introduces miR-138 as a negative regulator of CCDN1 in the progression of PCa with an inhibitory impact on the proliferation rate of prostate cancer (PCa) cell lines. This regulatory mechanism could be utilized for the design and target selection of remedial miRNA-based approaches.
2
Li, Weijian, Gaohuang Chen, Zhenyu Feng, Baoyi Zhu, Lilin Zhou, Yuying Zhang, Junyan Mai, Chonghe Jiang, and Jianwen Zeng. "YTHDF1 promotes the proliferation, migration, and invasion of prostate cancer cells by regulating TRIM44." Genes & Genomics 43, no. 12 (October 22, 2021): 1413–21. http://dx.doi.org/10.1007/s13258-021-01175-z.
Повний текст джерелаАнотація:
Abstract Background Prostate cancer (PCa) is one of the most common malignancies in men. YTHDF1 may play an important role in promoting PCa progression, but there is no reports to date on YTHDF1 function in PCa. Objective This study explored whether YTHDF1 could regulate TRIM44 in PCa cells. Methods By querying the TCGA database, we evaluated YTHDF1 expression in PCa, the OS and DFS of YTHDF1, and the correlation between YTHDF1 and TRIM44 in PCa. We constructed vectors to interfere with YTHDF1 expression and overexpress TRIM44 to examine the role of YTHDF1 and TRIM44 in PCa cells. Differentially expressed mRNAs were identified by mRNA sequencing. The levels of YTHDF1, TRIM44, LGR4, SGTA, DDX20, and FZD8 were measured by qRT-PCR and WB was used to determine YTHDF1 and TRIM44 expression. A CCK-8 assay was used to assess cell proliferation. A Transwell chamber assay was used measure cell migration and invasion ability. Results YTHDF1 was highly expressed in both Pca tissues and cells. PCa patient prognosis with high YTHDF1 expression was relatively poor. Cell function experiments showed that inhibiting YTHDF1 expression decreased cell proliferation, migration, and invasion. RNA sequencing analysis revealed that YTHDF1 may promote PCa cell proliferation, migration, and invasion by modulating TRIM44 expression. Cell function experiments further verified that YTHDF1 promoted PCa cell proliferation, migration, and invasion by regulating TRIM44. Conclusions YTHDF1 enhances PCa cell proliferation, migration, and invasion by regulating TRIM44.
3
SCHECHTER, NEIL L., NEIL L. FREDERICK, B. BERRIEN, and SHOSHANA M. KATZ. "PCA FOR ADOLESCENTS IN SICKLE-CELL CRISIS." AJN, American Journal of Nursing 88, no. 5 (May 1988): 719–24. http://dx.doi.org/10.1097/00000446-198805000-00028.
Повний текст джерела
4
Chen, Zhong-Jun, You-Ji Yan, Hao Shen, Jia-Jie Zhou, Guang-Hua Yang, Yi-Xiang Liao, Jin-Min Zeng, and Tao Yang. "miR-192 Is Overexpressed and Promotes Cell Proliferation in Prostate Cancer." Medical Principles and Practice 28, no. 2 (December 13, 2018): 124–32. http://dx.doi.org/10.1159/000496206.
Повний текст джерелаАнотація:
Objective: Prostate cancer (PCa) is one of the most prevalent types of cancer among men worldwide. The incidence of PCa is increasing in China. Therefore, there is an urgent need to identify novel diagnostic and prognostic markers for PCa to improve the treatment of the disease. Methods: The Cancer Genome Atlas (TCGA) and GEO database were used to analyze the expression of miR-192, and the relationship between miR-192 and the clinical features of patients with PCa. Cell cycle and cell proliferation assay were used to detect the functional roles of miR-192 in PCa. Bioinformatic analysis for miR-192–5p was performed using gene ontology and KEGG analysis. Results: By analyzing the dataset of TCGA, we found that miR-192 was overexpressed in PCa samples compared to normal tissues and was upregulated in high-grade PCa compared to low-grade PCa. We also observed that higher miR-192 expression was associated with a shorter biochemical recurrence-free survival time. Our results also demonstrated that miR-192 promoted PCa cell proliferation and cell cycle progression. Conclusion: These results suggest that miR-192 may be considered for use as a potential diagnostic and therapeutic target of PCa.
5
Franko, Andras, Lucia Berti, Alke Guirguis, Jörg Hennenlotter, Robert Wagner, Marcus O. Scharpf, Martin Hrabĕ de Angelis, et al. "Characterization of Hormone-Dependent Pathways in Six Human Prostate-Cancer Cell Lines: A Gene-Expression Study." Genes 11, no. 10 (October 7, 2020): 1174. http://dx.doi.org/10.3390/genes11101174.
Повний текст джерелаАнотація:
Prostate cancer (PCa), the most incident cancer in men, is tightly regulated by endocrine signals. A number of different PCa cell lines are commonly used for in vitro experiments, but these are of diverse origin, and have very different cell-proliferation rates and hormone-response capacities. By analyzing the gene-expression pattern of main hormone pathways, we systematically compared six PCa cell lines and parental primary cells. We compared these cell lines (i) with each other and (ii) with PCa tissue samples from 11 patients. We found major differences in the gene-expression levels of androgen, insulin, estrogen, and oxysterol signaling between PCa tissue and cell lines, and between different cell lines. Our systematic characterization gives researchers a solid basis to choose the appropriate PCa cell model for the hormone pathway of interest.
6
Chien, Ju-Huei, Shan-Chih Lee, Kai-Fu Chang, Xiao-Fan Huang, Yi-Ting Chen, and Nu-Man Tsai. "Extract of Pogostemon cablin Possesses Potent Anticancer Activity against Colorectal Cancer Cells In Vitro and In Vivo." Evidence-Based Complementary and Alternative Medicine 2020 (September 9, 2020): 1–11. http://dx.doi.org/10.1155/2020/9758156.
Повний текст джерелаАнотація:
Pogostemon cablin (PCa), an herb used in traditional Chinese medicine, is routinely used in the amelioration of different types of gastrointestinal discomfort. However, the mechanisms underlying the cancer suppression activity of PCa in colorectal cancer (CRC) cells have yet to be clarified. The aim of this study was to investigate the anticancer effects of PCa, specifically the induction of apoptosis in CRC cells. The growth inhibition curve of CRC cells following exposure to PCa was detected by an MTT assay. Moreover, PCa combined with 5-FU revealed a synergic effect of decreased cell viability. PCa inhibited cell proliferation and induced cell cycle arrest at the G0/G1 phase and cell apoptosis through regulation of associated protein expression. An in vivo study showed that PCa suppressed the growth of CRC via induction of cell apoptosis with no significant change in body weight or organ histology. Our results demonstrated that PCa inhibits the growth of CRC cells and induces apoptosis in vitro and in vivo, which suggests the potential applicability of PCa as an anticancer agent.
7
Zhang, Cunming, Song Chen, Lide Song, Haibo Ye, and Junwei Wang. "Krüppel-like factor 8 promotes aerobic glycolysis in prostate cancer cells by regulating AKT/mTOR signaling pathway." Tropical Journal of Pharmaceutical Research 19, no. 10 (November 25, 2020): 2091–96. http://dx.doi.org/10.4314/tjpr.v19i10.11.
Повний текст джерелаАнотація:
Purpose: To investigate the effects of Krüppel-like factor 8 (KLF8) in prostate cancer (PCa) cell viability and glycolysis, and explore its role as a regulatory factor.Methods: Immunoblot assays were conducted to assess the expression of KLF8 and proteins in AKT/mTOR pathway in PCa cell lines PC-3 and DU145. Cell Counting Kit-8 assays were performed to assess the effect of KLF8 on PCa cell viability. The glycolysis capacity of PCa cells was determined by measuring the levels of glucose intake, lactic acid production, and cellular ATP levels.Results: Depletion of KLF8 decreased the survival of PCa cells in vitro (p < 0.05). KLF8 depletion also inhibited aerobic glucose metabolism in PCa cells (p < 0.05). Further studies confirmed that KLF8 contributed to the growth and glycolysis of PCa cells via the regulation of AKT/mTOR pathway.Conclusion: KLF8 regulates glycolysis in PCa cells by regulating AKT/mTOR signaling pathway and is thus a promising therapeutic target for PCa treatment.
Keywords: Krüppel-like factor 8 (KLF8), Prostate cancer (PCa), Aerobic glucose, AKT/mTOR signaling pathway, Therapeutic target
8
Poluri, Raghavendra T. K., Virginie Paquette, Éric P. Allain, Camille Lafront, Charles Joly-Beauparlant, Cindy Weidmann, Arnaud Droit, Chantal Guillemette, Martin Pelletier, and Étienne Audet-Walsh. "KLF5 and NFYA factors as novel regulators of prostate cancer cell metabolism." Endocrine-Related Cancer 28, no. 4 (April 2021): 257–71. http://dx.doi.org/10.1530/erc-20-0504.
Повний текст джерелаАнотація:
Prostate cancer (PCa) cells rely on the androgen receptor (AR) signaling axis to reprogram metabolism to sustain aberrant proliferation. Whether additional transcription factors participate to this reprogramming remains mostly unknown. To identify such factors, DNA motif analyses were performed in the promoter and regulatory regions of genes sensitive to androgens in PCa cells. These analyses identified two transcription factors, KLF5 and NFYA, as possibly associated with PCa cell metabolism. In clinical datasets, KLF5 and NFYA expression levels were associated with disease aggressiveness, being significantly decreased and increased, respectively, during PCa progression. Their expression was next investigated by qPCR and Western blot in human PCa cell models, revealing a positive regulation of KLF5 by androgens and a correlation between NFYA and AR protein expression status. siRNA-mediated knockdown of KLF5 increased human PCa cell proliferation rate in AR-positive cell models, suggesting a tumor suppressor function. Live-cell metabolic assays showed that knockdown of KLF5 promoted mitochondrial respiration, a key metabolic pathway associated with PCa progression. The opposite was observed for knockdown of NFYA regarding proliferation and respiration. RNA-seq analyses following the knockdown of either KLF5 and NFYA confirmed that both factors regulated distinct metabolic gene signatures, as well as other gene signatures, explaining their differential impact on PCa cell proliferation and metabolism. Overall, our findings identify KLF5 and NFYA as novel regulators of PCa cell metabolism.
9
Wang, Qinghua, Zelin Liu, Guanzhong Zhai, Xi Yu, Shuai Ke, Haoren Shao, and Jia Guo. "Overexpression of GATA5 Inhibits Prostate Cancer Progression by Regulating PLAGL2 via the FAK/PI3K/AKT Pathway." Cancers 14, no. 9 (April 21, 2022): 2074. http://dx.doi.org/10.3390/cancers14092074.
Повний текст джерелаАнотація:
Background: Prostate cancer (PCa) is a malignancy with high incidence and the principal cause of cancer deaths in men. GATA binding protein 5 (GATA5) belongs to the GATA gene family. GATA5 has a close association with carcinogenesis, but the role of GATA5 in PCa remains poorly understood. The aim of our present study was to probe into the effect of GATA5 on PCa progression and to elucidate the involved mechanism. Methods: The expression of GATA5 was detected in both PCa samples and PCa cell lines. GATA5 overexpression, PLAGL2 knockdown, and overexpression cell models were generated, then Western blotting experiments were utilized to validate the efficiency of transfection. The effects of GATA5 on PCa cell proliferation, metastasis, apoptosis, cell cycle progression, and EMT were detected in vitro or in vivo. Furthermore, the mechanism by which GATA5 inhibits prostate cancer progression through regulating PLAGL2 via the FAK/PI3K/AKT pathway was also explored. Results: GATA5 expression was downregulated in PCa samples and cell lines. GATA5 overexpression inhibited PCa cell proliferation and metastasis but increased the rate of apoptosis. In addition, we confirmed that GATA5 inhibited prostate cancer progression, including EMT, by regulating PLAGL2 via the FAK/PI3K/AKT pathway. Conclusion: We demonstrated that GATA5, as a tumor suppressor in PCa, inhibits PCa progression by regulating PLAGL2. These results showed that the GATA5/PLAGL2/FAK/PI3K/AKT pathway may become a new therapeutic direction for the treatment of PCa.
10
Shi, Jian, Lian Zhao, Brittany Duncan, Jie Su, Jale Manzo, He Liu та Yuan-Shan Zhu. "Osteoblast-Induced Prostate Cancer Cell Migration and Invasion Is Mediated Through TGF-β1/SMAD2 Signal Pathway and Blocked by 17α-Estradiol". Journal of the Endocrine Society 5, Supplement_1 (1 травня 2021): A1029. http://dx.doi.org/10.1210/jendso/bvab048.2105.
Повний текст джерелаАнотація:
Abstract Prostate cancer (PCa) is curable if it is diagnosed and treated in localized and regional stage. However, PCa outcome is poor once it has distant metastasis. Approximately 70% to 100% of PCa deaths have bone metastasis, which may be associated with a specific bone microenvironment. In this study, we investigated the effect and molecular mechanism of osteoblast cells on stimulation of PCa cell migration and invasion and examined the effectiveness of 17α-estradiol on blocking osteoblast-induced PCa cell migration and invasion using in vitro cell analysis. PCa cells (PC3, LNCaP and DU145), osteoblast hFOB, kidney CV-1, breast tumor MCF-7 and liver cancer Huh-7 cells (ATCC) were cultured in RMPI-1640 or DMEM media supplemented with or without fetal bovine serum (FBS) at 37 oC in a 5% CO2-humidified incubator. hFOB condition media (HCM) without FBS were collected at different times of hFOB cell culture. Transwell and wound-healing experiments were used to determine PCa cell migration and invasion. Cell migration and invasion in PC3, DU-145 and LNCaP PCa cells were markedly promoted by co-culturing hFOB osteoblast cells or HCM, but not by cells or condition media originated from kidney (CV-1), liver (Huh-7) and breast (MCF-7). Compared to other non-osteoblast cell conditioned media, HCM had much higher levels of several cytokines and chemokines including tumor growth factor (TGF) β1. Both HCM and TGF-β1 produced a dose- and time-dependent induction of PCa cell migration and invasion as well as SMAD2 phosphorylation without altering cell proliferation. These HCM and TGF-β1 effects were inhibited by a specific TGFβ receptor inhibitor, LY2157299, as well as by 17α-estradiol in a dose-dependent manner. Most intriguing, 17α-estradiol significantly inhibited the HCM and TGF-β1-induced PCa cell migration and invasion at very low nanomolar concentrations, presumably mediated through estrogen receptor β. These findings suggest that TGF-β1 is a major factor in mediating hFOB cell stimulation of PCa cell migration and invasion, and 17α-estradiol is a potential agent to block PCa cell bone metastasis, probably through inhibition of TGF-β1/SMAD2 signal pathway.
11
Cheng, Siyuan, Lin Li, and Xiuping Yu. "Abstract 1452: Big data analysis revealed signalling activity and key regulators in human prostate cancer cell lines." Cancer Research 83, no. 7_Supplement (April 4, 2023): 1452. http://dx.doi.org/10.1158/1538-7445.am2023-1452.
Повний текст джерелаАнотація:
Abstract Background: Human prostate cancer (PCa) cell lines are the most used models for research. The commonly used PCa cell lines can be roughly categorized into 3 groups: androgen receptor (AR)+, neuroendocrine (NE)+ and double negative (AR- NE-) cell lines. However, although these cell lines have been extensively used in PCa research since their establishment decades ago, a global molecular characterization of these cell lines is still lacking, especially in the aspect of cell signaling activity and their clinical relevance, which requires a large scale of data mining. Methods: The RNA-seq, DNA-seq and proteomic datasets were gathered from public cohort and our lab’s collection. From these data, a PCa cell line multi-omics database (PCMD) was established. Single sample gene set enrichment analysis (ssGSEA) was used to reveal the signaling pathways enriched in each PCa cell line. Additionally, human PCa patient single cell RNAseq data-based deconvolution and human PCa patient bulk RNAseq data-based nearest-neighbor (NN) graph analysis were used to evaluate the clinical relevance of each PCa cell line. The DNA-seq, ATAC-seq, DNase HS-seq and Bisulfite-seq datasets were used to annotate the key genes. Results: The PCMD database was established by compiling more than 1000 RNASeq datasets derived from various PCa cell lines. The important signaling pathways and transcription factors were revealed for each PCa cell line. Further, the cell lines were annotated with relative clinical stages. Additionally, an interactive webApp was established for scientists to explore and visualize PCMD data. Conclusion: our research characterized PCa cell lines using unbiased strategies and large sample number. It is our hope that this study would aid researchers to develop hypothesis and choose appropriate cell line to use. Funding: This study is supported by: Feist-Weiller Cancer Center, LSU Health Shreveport. Citation Format: Siyuan Cheng, Lin Li, Xiuping Yu. Big data analysis revealed signalling activity and key regulators in human prostate cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1452.
12
Zhang, Shuxian, Qingqing Li, Huixiao Yuan, Ling Ren, Xuyang Liang, Shouying Li, Shengxiang Lv, and Hua Jiang. "Solute Carrier Family 35 Member F2 Regulates Cisplatin Resistance and Promotes Malignant Progression of Pancreatic Cancer by Regulating RNA Binding Motif Protein 14." Journal of Oncology 2022 (May 27, 2022): 1–8. http://dx.doi.org/10.1155/2022/5091154.
Повний текст джерелаАнотація:
We aimed to explore the role of Solute Carrier Family 35 Member F2 (SLC35F2) in pancreatic cancer (PCa) and to further study whether SLC35F2 regulates cisplatin resistance of PCa cells through the modulation of RNA binding motif protein 14 (RBM14) expression. SLC35F2 expression in 60 pairs of PCa tissues and adjacent ones was studied by RT-PCR analysis. Meanwhile, SLC35F2 expression levels in PCa cell lines were also evaluated by qPCR assay. In addition, SLC35F2 knockdown models were constructed in PCa cisplatin-resistant cells. Furthermore, we determined the interaction between SLC35F2 and RBM14 via luciferase assay. The findings of the present study demonstrated that SLC35F2 was significantly upregulated in PCa tissues. High level of SLC35F2 indicated higher incidence of metastasis and shorter survival rates. In vitro cell experiments revealed that knockdown of SLC35F2 suppressed cell invasion and metastasis capacity of cisplatin-resistant PCa cell lines PANC-1/DDP and CFPAC-1/DDP. It was also suggested that the key protein RBM14 in the SLC35F2 knockdown group was remarkably reduced. SLC35F2 can bind to RBM14 specifically. Overexpression of RBM14 partially reversed the effects of knockdown of SLC35F2 on the development of PCa. SLC35F2 expression in PCa tissues and cell lines is remarkably increased. In addition, it was also suggested that SLC35F2 may regulate cisplatin resistance of PCa cells through modulating RBM14 expression. In conclusion, it is conceivable from the study that SLC35F2 was remarkably upregulated in PCa and promoted the malignancy of PCa via regulating RBM14.
13
Markowitsch, Sascha D., Kira M. Juetter, Patricia Schupp, Kristine Hauschulte, Olesya Vakhrusheva, Kimberly Sue Slade, Anita Thomas, et al. "Shikonin Reduces Growth of Docetaxel-Resistant Prostate Cancer Cells Mainly through Necroptosis." Cancers 13, no. 4 (February 20, 2021): 882. http://dx.doi.org/10.3390/cancers13040882.
Повний текст джерелаАнотація:
The prognosis for advanced prostate carcinoma (PCa) remains poor due to development of therapy resistance, and new treatment options are needed. Shikonin (SHI) from Traditional Chinese Medicine has induced antitumor effects in diverse tumor entities, but data related to PCa are scarce. Therefore, the parental (=sensitive) and docetaxel (DX)-resistant PCa cell lines, PC3, DU145, LNCaP, and 22Rv1 were exposed to SHI [0.1–1.5 μM], and tumor cell growth, proliferation, cell cycling, cell death (apoptosis, necrosis, and necroptosis), and metabolic activity were evaluated. Correspondingly, the expression of regulating proteins was assessed. Exposure to SHI time- and dose-dependently inhibited tumor cell growth and proliferation in parental and DX-resistant PCa cells, accompanied by cell cycle arrest in the G2/M or S phase and modulation of cell cycle regulating proteins. SHI induced apoptosis and more dominantly necroptosis in both parental and DX-resistant PCa cells. This was shown by enhanced pRIP1 and pRIP3 expression and returned growth if applying the necroptosis inhibitor necrostatin-1. No SHI-induced alteration in metabolic activity of the PCa cells was detected. The significant antitumor effects induced by SHI to parental and DX-resistant PCa cells make the addition of SHI to standard therapy a promising treatment strategy for patients with advanced PCa.
14
Shen, Hao, Yong-Lian Guo, Guo-Hao Li, Wei Zhao, and Ling Zhang. "Gene Expression Analysis Reveals Key Genes and Signalings Associated with the Prognosis of Prostate Cancer." Computational and Mathematical Methods in Medicine 2021 (August 28, 2021): 1–13. http://dx.doi.org/10.1155/2021/9946015.
Повний текст джерелаАнотація:
It is urgent to identify novel biomarkers for prostate cancer (PCa) prognosis and to understand the mechanisms regulating the tumorigenesis for PCa treatment. In this study, GSE17951 and TCGA were used to identify the differentially expressed genes (DEGs). Our study demonstrated that 1533 genes with increased expression and 2301 genes with decreased expression in PCa. Bioinformatics analysis data indicated that these up-regulated genes had an association with the modulation of mitotic nuclear division, sister chromatid cohesion, cell division, and cell cycle. Additionally, our results revealed downregulated genes took part in modulating extracellular matrix organization, angiogenesis, signal transduction, and Ras signaling pathway. Hub upregulated and downregulated PPI networks were identified by protein-protein interaction (PPI) network analysis and MCODE analysis. Of note, 12 cell cycle regulators, comprising CCNB1, CCNB2, PLK1, TTK, AURKA, CDC20, BUB1, PTTG1, CDC45, CDC25C, CCNA2, and BUB1B, were demonstrated to function crucially in PCa development. By detecting their expression in PCa cell lines, we confirmed that these cell cycle regulator expressions were heightened in PCa cells. GEPIA databases analysis showed that higher expression of these cell cycle regulators was correlated to shorter disease-free survival (DFS) time in PCa samples. Our findings collectively suggested targeting cell cycle pathways may offer novel prognosis and treatment biomarkers for PCa.
15
Wang, Peiyu, Ligang Zhang, Shuiping Yin, Yuchen Xu, Sheng Tai, L. i. Zhang, and Chaozhao Liang. "hsa_circ_0062019 promotes the proliferation, migration, and invasion of prostate cancer cells via the miR-195-5p/HMGA2 axis." Acta Biochimica et Biophysica Sinica 53, no. 7 (May 6, 2021): 815–22. http://dx.doi.org/10.1093/abbs/gmab058.
Повний текст джерелаАнотація:
Abstract Circular RNA (circRNA) is a new class of non-coding RNA. It was reported that circRNA involves in the metastasis of cancer. The aim of this study is to explore the role and mechanism of circRNA hsa_circ_0062019 in the development of prostate cancer (PCa). Our results showed that hsa_circ_0062019 was highly expressed in PCa cell lines. Cell Counting Kit-8 assay revealed that upregulation of hsa_circ_0062019 boosted PCa cell proliferation, and silencing of hsa_circ_0062019 inhibited cell proliferation. Meanwhile, transwell assay proved that upregulation of hsa_circ_0062019 facilitated PCa cell invasion and migration, while downregulation of hsa_circ_0062019 inhibited these malignant phenotypes. Furthermore, luciferase reporter assay proved the binding of hsa_circ_0062019 with miR-195-5p and the binding between miR-195-5p and high mobility group AT-hook 2 (HMGA2), suggesting that hsa_circ_0062019 promoted the expression of HMGA2 by sponging miR-195-5p. In addition, our results revealed that the hsa_circ_0062019-induced PCa cell malignant phenotypes were notably reversed by the downregulation of HMGA2. Overall, our study demonstrated that hsa_circ_0062019 promoted PCa cell proliferation, migration, and invasion via upregulation of HMGA2 expression by sponging miR-195-5p. Our study proved a novel molecular mechanism of PCa development and provided a potential target for the treatment of PCa.
16
Abo, Muthana Al, Daniel J. George, Zefeng Wang, Steven R. Patierno, Jennifer A. Freedman, and Alice Jiang. "Abstract 1554: LIM Domain 7 (LMO7) splice variant influences prostate cancer biology." Cancer Research 84, no. 6_Supplement (March 22, 2024): 1554. http://dx.doi.org/10.1158/1538-7445.am2024-1554.
Повний текст джерелаАнотація:
Abstract LIM Domain 7 (LMO7) has been shown to participate in cell-cell junction formation through interaction with afadin and α-actinin. It has also been reported to collaborate with Rho kinase to regulate actin filament formation and to activate the Rho-myocardin-related transcription factor serum response factor pathway. Additionally, LMO7 itself may function as a transcription factor, regulating the expression of genes involved in Epithelial Mesenchymal Transition (EMT). Alternative splicing of LMO7 has the potential to modulate its function. Previously, we reported LMO7 as a target that is alternatively spliced in prostate cancer (PCa) between self-reported Black and White patients. In addition, by analyzing expression of LMO7 splice variants in The Cancer Genome Atlas (TCGA) data, we previously reported increased expression of a LMO7 splice variant skipping exon 12 in breast, lung and liver cancer compared with paired normal tissues. In the present study, we found that LMO7 is downregulated in metastatic PCa specimens within the Stand Up To Cancer cohort. To investigate the functional impact of expression of the LMO7 splice variant skipping exon 12 in PCa, we utilized CRISPR-Cas9 methodology to delete LMO7 exon 12 in PCa cells and assessed resulting alterations in PCa cell biology. The LMO7 exon 12 deleted PC3 PCa cells exhibited enhanced migratory potential compared with parental PCa cells. An Immunofluorescence (IF) assay showed weak staining of cell-cell junctions in LMO7 exon 12 deleted PCa cells compared with parental PCa cells. Moreover, IF staining showed retardation in f-actin in LMO7 exon 12 deleted PCa cells compared with parental PCa cells. As E-Cadherin is often inhibited during EMT, we assessed the level of E-Cadherin by western blot and real-time polymerase chain reaction (PCR). These analyses revealed that E-Cadherin protein as well as messenger RNA is suppressed in LMO7 exon 12 deleted PCa cells compared with parental PCa cells. These findings suggest a role for skipping of LMO7 exon 12 in disrupting PCa cell-cell junctions, down-regulating E-Cadherin in PCa and enhancing PCa cell migratory potential, consistent with EMT. Citation Format: Muthana Al Abo, Daniel J. George, Zefeng Wang, Steven R. Patierno, Jennifer A. Freedman, Alice Jiang. LIM Domain 7 (LMO7) splice variant influences prostate cancer biology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1554.
17
Scott, Julia S., Reuben Young, Swati Irani, Jonas Dehairs, Stephen Blanksby, Johannes V. Swinnen, Zeyad D. Nassar, and Lisa M. Butler. "Abstract A031: A fat lot of good: A novel monounsaturated fatty acid promotes prostate cancer growth and survival." Cancer Research 83, no. 11_Supplement (June 2, 2023): A031. http://dx.doi.org/10.1158/1538-7445.prca2023-a031.
Повний текст джерелаАнотація:
Abstract Advanced prostate cancer (PCa) is currently incurable, and development of novel treatments requires a greater understanding of key pathways that are altered during PCa progression. We have focussed on fatty acid metabolism, as the major source of energy for PCa cells, and have implicated a monounsaturated fatty acid (MUFA), cis-vaccenic acid (cVA), as a critical regulator of PCa cell homeostasis. Production of cVA requires stearoyl-CoA desaturase 1 (SCD1), the enzyme attributed to general MUFA production, and whose activity is important in a range of cancer types. Nonetheless, the specific role of cVA has not previously been studied, in PCa nor cancer more generally. To elucidate the role of cVA in PCa more precisely, we used SCD1 inhibition to study PCa responses to broad MUFA depletion and specific MUFA supplementation, comparing the responses of cVA with its more common structural isomer oleate. To accomplish these aims, we utilised cell line models of PCa (LNCaP, MR49F and V16D) and a benign prostate cell line (PNT1A) to perform cell viability, lipidomic and flow cytometric assays. In addition, responses in clinically-relevant patient-derived tumor explants were measured by proliferative (Ki67) and cell death (CC3) marker staining. Pharmacological SCD1 inhibition (SCDi; A939572) decreased cell viability and increased cell death in PCa cell lines and patient-derived tumor explants, while only minimally affecting the benign prostate cell line PNT1A. Phenotypically, analysis of mitochondrial function and lipidomic changes under SCDi suggested a role for MUFAs in regulating mitochondrial membrane composition via cardiolipins, and oxidative stress levels. This in turn has the potential to regulate cell death, control tumor burden, and influence overall PCa patient survival. Supplementation of cVA or oleate under SCDi demonstrated that only cVA was successful at rescuing cell viability, and cVA, but not oleate, could rescue changes observed in mitochondrial-related lipids, suggesting that cVA regulation of mitochondrial function was a major determinant of its effect on cell viability. Additionally, cVA alone dose-dependently increased PCa cell viability, implicating cVA as an important oncogenic factor. Together, these data identify cVA as a novel substrate required for PCa cell viability, likely via regulation of mitochondrial homeostasis and associated cell death pathways. In summary, this research has revealed more precise insights into the oncogenic effects of an overlooked MUFA, cVA, in PCa, and may uncover new druggable targets that are more selective, to improve treatment options for advanced PCa. Citation Format: Julia S. Scott, Reuben Young, Swati Irani, Jonas Dehairs, Stephen Blanksby, Johannes V. Swinnen, Zeyad D. Nassar, Lisa M. Butler. A fat lot of good: A novel monounsaturated fatty acid promotes prostate cancer growth and survival [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A031.
18
Mora, Benjamin C., Neil E. Fleshner, Laurence H. Klotz, and Vasundara Venkateswaran. "The Effects of Serum from Prostate Cancer Patients with Elevated Body Mass Index on Prostate Cancer Cells in Vitro." Lipid Insights 8 (January 2015): LPI.S23135. http://dx.doi.org/10.4137/lpi.s23135.
Повний текст джерелаАнотація:
We examined whether serum from obese, compared to non-obese, PCa (prostate cancer) patients creates a growth-enhancing tumor micro-environment in vitro. Serum from 80 subjects was divided into four groups: normal weight men with and without PCa and overweight/obese men with and without PCa. Cell proliferation, migration, and invasion were measured in LNCaP, and PC3 cells treated with patient serum were obtained from the above groups. The results reveal that proliferation of LNCaP cells was significantly ( P = 0.05) greater with serum from non-obese (mean = 1.26 ± 0.20) compared to that from obese patients (mean = 1.16 ± 0.19). Serum from obese PCa patients compared to non-obese PCa patients induced significantly greater amounts of cell migration ( P < 0.01) in PC3 cells. Serum from obese patients induced significantly ( P < 0.01) lower amounts of cell invasion (mean = 8.2 ± 4.5) compared to non-obese patients (mean = 18.1 ± 5.0) when treated on PC3 cells. Serum TNF-α (tumor necrosis factor alpha) levels correlated with LNCaP cell proliferation in vitro in non-obese PCa ( P < 0.01) and non-obese control groups ( P = 0.05). All statistical calculations controlled for age, since the PCa patient groups were significantly older than the control groups ( P < 0.01). In conclusion, serum from obese PCa patients induced greater PCa cell migration and lower cell proliferation and invasion in vitro.
19
Torres-Estay, Verónica, Michalis Mastri, Spencer Rosario, Patricia Fuenzalida, Carolina E. Echeverría, Emilia Flores, Anica Watts, et al. "The Differential Paracrine Role of the Endothelium in Prostate Cancer Cells." Cancers 14, no. 19 (September 29, 2022): 4750. http://dx.doi.org/10.3390/cancers14194750.
Повний текст джерелаАнотація:
The survival of patients with solid tumors, such as prostate cancer (PCa), has been limited and fleeting with anti-angiogenic therapies. It was previously thought that the mechanism by which the vasculature regulates tumor growth was driven by a passive movement of oxygen and nutrients to the tumor tissue. However, previous evidence suggests that endothelial cells have an alternative role in changing the behavior of tumor cells and contributing to cancer progression. Determining the impact of molecular signals/growth factors released by endothelial cells (ECs) on established PCa cell lines in vitro and in vivo could help to explain the mechanism by which ECs regulate tumor growth. Using cell-conditioned media collected from HUVEC (HUVEC-CM), our data show the stimulated proliferation of all the PCa cell lines tested. However, in more aggressive PCa cell lines, HUVEC-CM selectively promoted migration and invasion in vitro and in vivo. Using a PCa-cell-line-derived xenograft model co-injected with HUVEC or preincubated with HUVEC-CM, our results are consistent with the in vitro data, showing enhanced tumor growth, increased tumor microvasculature and promoted metastasis. Gene set enrichment analyses from RNA-Seq gene expression profiles showed that HUVEC-CM induced a differential effect on gene expression when comparing low versus highly aggressive PCa cell lines, demonstrating epigenetic and migratory pathway enrichments in highly aggressive PCa cells. In summary, paracrine stimulation by HUVEC increased PCa cell proliferation and tumor growth and selectively promoted migration and metastatic potential in more aggressive PCa cell lines.
20
Salamini-Montemurri, Martín, Ángel Vizoso-Vázquez, Aida Barreiro-Alonso, Lidia Lorenzo-Catoira, Esther Rodríguez-Belmonte, María-Esperanza Cerdán, and Mónica Lamas-Maceiras. "The Effect of HMGB1 and HMGB2 on Transcriptional Regulation Differs in Neuroendocrine and Adenocarcinoma Models of Prostate Cancer." International Journal of Molecular Sciences 25, no. 6 (March 7, 2024): 3106. http://dx.doi.org/10.3390/ijms25063106.
Повний текст джерелаАнотація:
Human high-mobility group-B (HMGB) proteins regulate gene expression in prostate cancer (PCa), a leading cause of oncological death in men. Their role in aggressive PCa cancers, which do not respond to hormonal treatment, was analyzed. The effects of HMGB1 and HMGB2 silencing upon the expression of genes previously related to PCa were studied in the PCa cell line PC-3 (selected as a small cell neuroendocrine carcinoma, SCNC, PCa model not responding to hormonal treatment). A total of 72% of genes analyzed, using pre-designed primer panels, were affected. HMGB1 behaved mostly as a repressor, but HMGB2 as an activator. Changes in SERPINE1, CDK1, ZWINT, and FN1 expression were validated using qRT-PCR after HMGB1 silencing or overexpression in PC-3 and LNCaP (selected as an adenocarcinoma model of PCa responding to hormonal treatment) cell lines. Similarly, the regulatory role of HMGB2 upon SERPINE1, ZWINT, FN1, IGFPB3, and TYMS expression was validated, finding differences between cell lines. The correlation between the expression of HMGB1, HMGB2, and their targets was analyzed in PCa patient samples and also in PCa subgroups, classified as neuroendocrine positive or negative, in public databases. These results allow a better understanding of the role of HMGB proteins in PCa and contribute to find specific biomarkers for aggressive PCa.
21
Vanneste, Domien, Jens Staal, Mira Haegman, Yasmine Driege, Marieke Carels, Elien Van Nuffel, Pieter De Bleser, Yvan Saeys, Rudi Beyaert, and Inna S. Afonina. "CARD14 Signalling Ensures Cell Survival and Cancer Associated Gene Expression in Prostate Cancer Cells." Biomedicines 10, no. 8 (August 18, 2022): 2008. http://dx.doi.org/10.3390/biomedicines10082008.
Повний текст джерелаАнотація:
Prostate cancer (PCa) is one of the most common cancer types in men and represents an increasing global problem due to the modern Western lifestyle. The signalling adapter protein CARD14 is specifically expressed in epithelial cells, where it has been shown to mediate NF-κB signalling, but a role for CARD14 in carcinoma has not yet been described. By analysing existing cancer databases, we found that CARD14 overexpression strongly correlates with aggressive PCa in human patients. Moreover, we showed that CARD14 is overexpressed in the LNCaP PCa cell line and that knockdown of CARD14 severely reduces LNCaP cell survival. Similarly, knockdown of BCL10 and MALT1, which are known to form a signalling complex with CARD14, also induced LNCaP cell death. MALT1 is a paracaspase that mediates downstream signalling by acting as a scaffold, as well as a protease. Recent studies have already indicated a role for the scaffold function of MALT1 in PCa cell growth. Here, we also demonstrated constitutive MALT1 proteolytic activity in several PCa cell lines, leading to cleavage of A20 and CYLD. Inhibition of MALT1 protease activity did not affect PCa cell survival nor activation of NF-κB and JNK signalling, but reduced expression of cancer-associated genes, including the cytokine IL-6. Taken together, our results revealed a novel role for CARD14-induced signalling in regulating PCa cell survival and gene expression. The epithelial cell type-specific expression of CARD14 may offer novel opportunities for more specific therapeutic targeting approaches in PCa.
22
Liu, Min, Chuanbing Xu, Huichao Dong, Dongshen Jia, Dongfang Hao, Ruozen Rong, and Yao Peng. "Iron Oxide Nanoparticles Carrying microRNA-124 Promote Ferroptosis in Treatment of Prostate Cancer." Journal of Biomedical Nanotechnology 20, no. 2 (February 1, 2024): 224–30. http://dx.doi.org/10.1166/jbn.2024.3782.
Повний текст джерелаАнотація:
Prostate cancer (PCa) is a common malignancy among men worldwide. Iron oxide (Fe3O4) nanoparticles (NPs) exhibit great potential in gene delivery and studies have noted the inhibitory effect of miR-124 on PCa cell growth. Herein, we identified the therapeutic effect of Fe3O4 NPs carrying miR-124 in PCa and clarified its mechanism of action in inhibiting progression of PCa. After preparation of Fe3O4 NPs carrying miR-124, human PCa cell line PC3 was treated with miR-124-Fe3O4 NPs when ferroptosis inducer FIN56, ferroptosis inhibitor Liproxstatin-1, Phosphatase and tensin homolog (PTEN) inhibitor SF1670 or PTEN activator Oroxin B were added for transfection. Afterwards, assays were conducted to evaluate PCa cell biological activities. Additionally, we determined expression of PTEN and AKT and ferroptosis-related protein GPX4 and SLC7A11 in each group. We confirmed anticancer effects of miR-124-Fe3O4 NPs in PCa, as they suppressed PC3 cell proliferation and migration, and induced apoptosis. Compared with miR-124-Fe3O4 + Liproxstatin-1 group, the expressions of GPX4 and SLC7A11 proteins in miR-124-Fe3O4 group were elevated. The advent of PTEN activator Oroxin B decreased proliferative ability of PCa cells, and SF1670 treatment decreased PTEN level and elevated AKT level. With highest apoptotic rate of PCa cells in miR-124-Fe3O4 + Oroxin B + FIN56 group, intervention of SF1670 or Liproxstatin-1 changed the cell viability, while Oroxin B caused decreased AKT level and increased level of ferroptosis-related proteins. miR-124-Fe3O4 NPs hinder PCa progression by promoting ferroptosis and cell apoptosis through regulation of PTEN/Akt pathway.
23
Zhang, Qiuyang, Sen Liu, Bing Zhang, Elizabeth Norton, S. Michal Jazwinski, Oliver Sartor, Chad Steele, and Asim B. Abdel-Mageed. "AGE-RELATED ELEVATED CD4+ T HELPER 17 CELL RESPONSE PROMOTES PROSTATE CANCER CELL GROWTH, MIGRATION, AND INVASION." Innovation in Aging 3, Supplement_1 (November 2019): S879. http://dx.doi.org/10.1093/geroni/igz038.3221.
Повний текст джерелаАнотація:
Abstract Age is the most important risk factor for prostate cancer (PCa). But, how age contributes to PCa remains unknown. Interleukin-17 (IL-17) -producing CD4+ T helper 17 (Th17) cells play a critical role in inflammatory diseases. It is often elevated in aging humans and mice, however, whether aging affects Th17 cell function and subsequent PCa risk increase is unclear. In this study, we investigated the role of CD4+ T cells in PCa cell growth during the aging process. Splenic T cells were isolated and purified into CD4+CD25- T cells from young and old mice, then cultured in the presence of plate-bound anti-CD3/anti-CD28. Four days later, the cells were re-stimulated with PMA and ionomycin in the presence of brefeldin A for 4 hours and then were collected and used for flow cytometry and/or qPCR. The supernatant (conditioned media) from young and old cultures was collected and used in subsequent experiments. Flow and qPCR results showed that 17-producing T cells and associated cytokines were significantly increased in old mice compared to young mice. When PCa cell lines (LNCaP, DU-145, and PC3) were treated by the conditioned media for 48 and 72 hours. The cell proliferation, migration, and invasion, as well as the activation of NF-B signaling in PCa cells, were significantly increased after exposure to the conditioned media from aged mice, compared to that from young mice. These results indicated that age-related CD4+ Th17 cell responses are elevated in mice in the aging process and play an important role in PCa growth.
24
Mei, Qiyuan, Xiaohu Chen, and Wei Liu. "Protocatechuic Acid Induces Apoptosis in Human Osteosarcoma Cells by Regulating P13K/AKT/ROS Pathway." Sains Malaysiana 51, no. 4 (April 30, 2022): 1167–79. http://dx.doi.org/10.17576/jsm-2022-5104-18.
Повний текст джерелаАнотація:
Previous investigations have demonstrated that protocatechuic acid (PCA) provides anti-tumour properties in different tumour cell types. It does, however, have an unknown cause on osteosarcoma cells. In this investigation, the underlying mechanism of the effect of PCA on osteosarcoma cells (MNNG or HOS) was investigated and established. The viability of the cell was assessed with the MTT test. Acridine orange/ethidium bromide staining and Western blot analysis were conducted for assessment of cell apoptosis. Western blot analysis was identified for cell cycle progression. In addition to establishing the above findings, the Western blot analysis demonstrated that PCA mediated osteosarcoma cellular apoptosis by triggering the apoptotic pathway of Caspase-9. Additionally, we found that PCA considerably stimulated osteosarcoma cell apoptosis and arrest of cell cycle proliferation by controlling a pathway involving P13K/Akt/ROS signalling. In short, we observed that PCA prevented the advancement of osteosarcoma through the stimulation of apoptosis in osteosarcoma cells. The mechanism underlying this study also showed that PCA generated effective anti-tumour activity on osteosarcoma cells by controlling the signalling pathways of P13K/Akt/ROS.
25
Champagne, Audrey, Imene Chebra, Pallavi Jain, Cassandra Ringuette Goulet, Annie Lauzier, Antoine Guyon, Bertrand Neveu, and Frédéric Pouliot. "An Extracellular Matrix Overlay Model for Bioluminescence Microscopy to Measure Single-Cell Heterogeneous Responses to Antiandrogens in Prostate Cancer Cells." Biosensors 14, no. 4 (April 5, 2024): 175. http://dx.doi.org/10.3390/bios14040175.
Повний текст джерелаАнотація:
Prostate cancer (PCa) displays diverse intra-tumoral traits, impacting its progression and treatment outcomes. This study aimed to refine PCa cell culture conditions for dynamic monitoring of androgen receptor (AR) activity at the single-cell level. We introduced an extracellular matrix-Matrigel (ECM-M) culture model, enhancing cellular tracking during bioluminescence single-cell imaging while improving cell viability. ECM-M notably tripled the traceability of poorly adherent PCa cells, facilitating robust single-cell tracking, without impeding substrate permeability or AR response. This model effectively monitored AR modulation by antiandrogens across various PCa cell lines. Single-cell imaging unveiled heterogeneous antiandrogen responses within populations, correlating non-responsive cell proportions with drug IC50 values. Integrating ECM-M culture with the PSEBC-TSTA biosensor enabled precise characterization of ARi responsiveness within diverse cell populations. Our ECM-M model stands as a promising tool to assess heterogeneous single-cell treatment responses in cancer, offering insights to link drug responses to intracellular signaling dynamics. This approach enhances our comprehension of the nuanced and dynamic nature of PCa treatment responses.
26
Wan, Xinhai, Paul G. Corn, Jun Yang, Nallasivam Palanisamy, Michael W. Starbuck, Eleni Efstathiou, Elsa M. Li Ning Tapia, et al. "Prostate cancer cell–stromal cell crosstalk via FGFR1 mediates antitumor activity of dovitinib in bone metastases." Science Translational Medicine 6, no. 252 (September 3, 2014): 252ra122. http://dx.doi.org/10.1126/scitranslmed.3009332.
Повний текст джерелаАнотація:
Bone is the most common site of prostate cancer (PCa) progression to a therapy-resistant, lethal phenotype. We found that blockade of fibroblast growth factor receptors (FGFRs) with the receptor tyrosine kinase inhibitor dovitinib has clinical activity in a subset of men with castration-resistant PCa and bone metastases. Our integrated analyses suggest that FGF signaling mediates a positive feedback loop between PCa cells and bone cells and that blockade of FGFR1 in osteoblasts partially mediates the antitumor activity of dovitinib by improving bone quality and by blocking PCa cell–bone cell interaction. These findings account for clinical observations such as reductions in lesion size and intensity on bone scans, lymph node size, and tumor-specific symptoms without proportional declines in serum prostate-specific antigen concentration. Our findings suggest that targeting FGFR has therapeutic activity in advanced PCa and provide direction for the development of therapies with FGFR inhibitors.
27
Salemi, Michele, Filippo Fraggetta, Antonio Galia, Pietro Pepe, Laura Cimino, Rosita A. Condorelli, and Aldo E. Calogero. "Cerebellar Degeneration-Related Autoantigen 1 (CDR1) Gene Expression in Prostate Cancer Cell Lines." International Journal of Biological Markers 29, no. 3 (July 2014): 288–90. http://dx.doi.org/10.5301/jbm.5000062.
Повний текст джерелаАнотація:
Prostate cancer (PCa) is the most frequent cancer among men in many developing countries, and the second leading cause of cancer-related death in men. A genetic component has been implicated in PCa onset and development. The cerebellar degeneration-related autoantigen 1 ( CDR1) gene, mapping in Xq26-q27.2, is expressed in cerebrum, cerebellum, heart, lung, liver, and kidney. In addition, CDR1 expression has been detected in neuroblastoma, renal carcinoma cell lines, and other cancer cell lines. In this study, we investigated the expression of the CDR1 gene in the LNCaP and PC-3 PCa cell lines, and in the PNT1A normal prostate cell line. CDR1 mRNA expression was evaluated by qRT-PCR. We found that the CDR1 gene was overexpressed in the LNCaP and PC-3 PCa cell lines as compared with the PNT1A normal prostate cell line. These data suggest that CDR1 could be a new biomarker for PCa identification.
28
Dehghani, Mehdi, Sedigheh Kianpour, Ana Zangeneh та Zohreh Mostafavi-Pour. "CXCL12 Modulates Prostate Cancer Cell Adhesion by Altering the Levels or Activities ofβ1-Containing Integrins". International Journal of Cell Biology 2014 (2014): 1–11. http://dx.doi.org/10.1155/2014/981750.
Повний текст джерелаАнотація:
The mechanisms by which prostate cancer (PCa) cell adhesion and migration are controlled during metastasis are not well understood. Here, we studied the effect of CXCL12 in PCa cell adhesion and spreading in DU145 and PC3 cell lines using as substrates collagen I, fibronectin (FN), and their recombinant fragments. CXCL12 treatment increasedβ1 integrin-dependent PC3 cell adhesion on FN which correlated with increased focal adhesion kinase activation. However neitherα5β1 norα4β1 subunits were involved in this adhesion. By contrast, CXCL12 decreased DU145 adhesion and spreading on FN by downregulatingα5 andβ1 integrin expression. To demonstrate the clinical relevance of CXCL12 in PCa, we measured CXCL12 levels in plasma by using ELISA and found that the chemokine is elevated in PCa patients when compared to controls. The high concentration of CXCL12 in patients suffering from PCa in comparison to those with benign disease or healthy individuals implicates CXCL12 as a potential biomarker for PCa. In addition these data show that CXCL12 may be crucial in controlling PCa cell adhesion on fibronectin and collagen I, possibly via crosstalk with integrin receptors and/or altering the expression levels of integrin subunits.
29
Colon, Leslimar Rios, Juliet Chijioke, Suryakant Niture, Zainab Afzal, Qi Qi, Anvesha Srivastava, Malathi Ramalinga, et al. "Abstract 5822: Leptin modulated microRNA-628-5p targets Jagged1 and inhibits prostate cancer hallmarks." Cancer Research 82, no. 12_Supplement (June 15, 2022): 5822. http://dx.doi.org/10.1158/1538-7445.am2022-5822.
Повний текст джерелаАнотація:
Abstract Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer and the second leading cause of cancer deaths in men. Obesity is a major risk factor for prostate cancer. Leptin is an obesity hormone that controls body weight by regulating energy intake and expenditure, and clinical studies have demonstrated a correlation between blood leptin levels and PCa development. MicroRNAs (miRs) are master regulators of cancer cell signaling, including in advanced PCa. We previously identified miR-628-5p as a potential biomarker in PCa patients that was downregulated in serum samples of men with PCa (Tumor Biol., 2014, 35: 4867). In this study, we investigated the link between the obesity hormone leptin and the functional role of miR-628-5p in PCa cell lines. We demonstrate that leptin downregulates the expression of miR-628-5p and increases cell proliferation and migration in PCa cells. Enforced expression of miR-628-5p inhibited cell proliferation in PCa cells. Further, miR-628-5p reduced PCa cell survival/migration/invasion/spheroids formation and cell stemness. Mechanistically, miR-628-5p binds with JAG1-3’UTR and inhibits the expression of Jagged-1 (JAG1). JAG1 inhibition by miR-628-5p also downregulated Notch signaling, decreased the expression of snail/slug, and modulated epithelial-mesenchymal transition and invasiveness in PC3 cells. Furthermore, miR-628-5p increased sensitivity towards enzalutamide and docetaxel by inducing cell apoptosis. Collectively our data suggested that miR-628-5p is a key regulator of PCa carcinogenesis modulated by adipokine leptin and offers a novel therapeutic opportunity to inhibit the growth of advanced PCa. Citation Format: Leslimar Rios Colon, Juliet Chijioke, Suryakant Niture, Zainab Afzal, Qi Qi, Anvesha Srivastava, Malathi Ramalinga, Habib Kedir, Patrice Cagle, Elena Arthur, Gagan Deep, Simeng Suy, Sean Collins, Deepak Kumar. Leptin modulated microRNA-628-5p targets Jagged1 and inhibits prostate cancer hallmarks [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5822.
30
Niture, Suryakant, Lucas Tricoli, Qi Qi, Sashi Gadi, Kala Hayes, and Deepak Kumar. "MicroRNA-99b-5p targets mTOR/AR axis, induces autophagy and inhibits prostate cancer cell proliferation." Tumor Biology 44, no. 1 (July 5, 2022): 107–26. http://dx.doi.org/10.3233/tub-211568.
Повний текст джерелаАнотація:
OBJECTIVES: MicroRNAs (miRNAs) are the small non-coding regulatory RNA molecules involved in gene regulation via base-pairing with complementary sequences in mRNAs. The dysregulation of specific miRNAs, such as miR-99b-5p (miR-99b), is associated with prostate cancer (PCa) progression. However, the mechanistic role of miR-99b in PCa remains to be determined. In this study, we aimed to investigate the functional and clinical significance of miR-99b in PCa. STUDY DESIGN: The expression of miR-99b and its downstream targets mTOR/AR in the PCa samples were analyzed by RT/qPCR. The effects of miR-99b overexpression/inhibition on PCa cell survival/proliferation, spheroid formation, and cell migration were examined by specific assays. Luciferase reporter assays were performed to determine the binding of miR-99b to 3′ untranslated region (UTR) of the mTOR gene. The effects of miR-99b on the expression of mTOR, AR, and PSA proteins, as well as on AKT/mTOR signaling, autophagy, and neuroendocrine differentiation markers were analyzed by western blotting. The expression of miR-99b, mTOR, AR, PSA in AR-negative PC3 and AR-positive LNCaP cells was analyzed by RT/qPCR. The effect of miR-99b on global gene expression in PC3 cells was analyzed by RNA-seq. RESULTS: The expression of miR-99b was downregulated in tumor samples from PCa patients, whereas the expression of mTOR and AR was upregulated. In PCa cell lines, overexpression of miR-99b inhibited cell proliferation and cell colony/spheroid formation; induced apoptosis, and increased sensitivity towards docetaxel (DTX). In contrast, inhibition of miR-99b by miR-99b inhibitor resulted in increased cell growth in PCa cells. Mechanistically, miR-99b inhibited the expression of the mammalian target of the rapamycin (mTOR) gene by binding to its 3′ UTR and induced autophagy. Furthermore, miR-99b inhibited androgen receptor (AR) activity in LNCaP cells and induced apoptosis. Activation of AR signaling by dihydrotestosterone (DHT) downregulated miR-99b expression and promoted cell PCa cell growth/survival, whereas inactivation of mTOR by rapamycin or AR by enzalutamide decreased miR-99b mediated PCa cell growth. CONCLUSION: Our data suggest that miR-99b functions as a tumor suppressor by targeting the mTOR/AR axis in PCa cells, implicating miR-99b as a novel biomarker and therapeutic target for PCa management.
31
Zhang, Haiyan, and Haixiang Guo. "Long non-coding RNA NORAD induces cell proliferation and migration in prostate cancer." Journal of International Medical Research 47, no. 8 (July 25, 2019): 3898–904. http://dx.doi.org/10.1177/0300060519862076.
Повний текст джерелаАнотація:
Objectives Prostate cancer (PCA) is the deadliest urological disease affecting men worldwide. Long noncoding RNA activated by DNA damage (NORAD) levels are increased in many cancer types, and induce cancer cell progression. However, little is known about the biological functions of NORAD in PCA. Methods In this work, the roles of NORAD in cell proliferation, migration, and apoptosis were examined by Cell Counting Kit-8, scratch wound, and annexin V-fluorescein isothiocyanate/propidium iodide staining assays, respectively, in PCA cell lines. Knockdown of NORAD was achieved by small interfering (si)RNA in PCA cell lines, and quantitative real-time PCR was used to detect the expression of NORAD. Results Cell proliferation and migration rates were significantly lower in the siNORAD group than in the wild-type group, while the apoptosis level was significantly higher in the siNORAD group compared with the wild-type group. Conclusions These results suggest that NORAD promotes the proliferation and migration of PCA cells and inhibits their apoptosis.
32
Li, Chang, Shuohui Gao, Xiaoping Li, Chang Li, and Lianjun Ma. "Procaine Inhibits the Proliferation and Migration of Colon Cancer Cells Through Inactivation of the ERK/MAPK/FAK Pathways by Regulation of RhoA." Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 28, no. 6 (March 16, 2020): 675–79. http://dx.doi.org/10.3727/096504021x16137463165406.
Повний текст джерелаАнотація:
Originally published in Volume 26, No. 2, pages 209–217, 2018 (doi:https://doi.org/10.3727/096504017X14944585873622) Colon cancer is one of the most lethal varieties of cancer. Chemotherapy remains as one of the principal treatment approaches for colon cancer. The anticancer activity of procaine (PCA), which is a local anesthetic drug, has been explored in different studies. In our study, we aimed to explore the anticancer effect of PCA on colon cancer and its underlying mechanism. The results showed that PCA significantly inhibited cell viability, increased the percentage of apoptotic cells, and decreased the expression level of RhoA in HCT116 cells in a dose-dependent manner (p < 0.05 or p < 0.01). Moreover, PCA increased the proportion of HCT116 cells in the G1 phase as well as downregulated cyclin D1 and cyclin E expressions (p < 0.05). In addition, we found that PCA remarkably inhibited cell migration in HCT116 cells (p < 0.01). However, all these effects of PCA on cell proliferation, apoptosis, and migration were significantly reversed by PCA + pc-RhoA (p < 0.05 or p < 0.01). PCA also significantly decreased the levels of p-ERK, p-p38MAPK, and p-FAK, but PCA + pc-RhoA rescued these effects. Furthermore, the ERK inhibitor (PD098059), p38MAPK inhibitor (SB203580), and FAK inhibitor (Y15) reversed these results. These data indicate that PCA inhibited cell proliferation and migration but promoted apoptosis as well as inactivated the ERK/MAPK/FAK pathways by regulation of RhoA in HCT116 cells.
33
Ionescu, Cristina-Anita, Mariana Aschie, Elena Matei, Georgeta Camelia Cozaru, Mariana Deacu, Anca Florentina Mitroi, Gabriela Isabela Baltatescu, et al. "Characterization of the Tumor Microenvironment and the Biological Processes with a Role in Prostatic Tumorigenesis." Biomedicines 10, no. 7 (July 12, 2022): 1672. http://dx.doi.org/10.3390/biomedicines10071672.
Повний текст джерелаАнотація:
Prostate intratumoral heterogeneity, driven by epithelial–mesenchymal plasticity, contributes to the limited treatment response, and it is therefore necessary to use the biomarkers to improve patient prognostic survival. We aimed to characterize the tumor microenvironment (T lymphocyte infiltration, intratumoral CD34, and KI-67 expressions) by immunohistochemistry methods and to study the biological mechanisms (cell cycle, cell proliferation by adhesion glycoproteins, cell apoptosis) involved in the evolution of the prostate tumor process by flow-cytometry techniques. Our results showed that proliferative activity (S-phase) revealed statistically significant lower values of prostate adenocarcinoma (PCa) and benign prostatic hyperplasia (BPH) reported at non-malignant adjacent cell samples (PCa 4.32 ± 4.91; BPH 2.35 ± 1.37 vs. C 10.23 ± 0.43, p < 0.01). Furthermore, 68% of BPH cases and 88% of patients with PCa had aneuploidy. Statistically increased values of cell proliferation (CD34+ CD61+) were observed in prostate adenocarcinoma and hyperplasia cases reported to non-malignant adjacent cell samples (PCa 28.79 ± 10.14; BPH 40.65 ± 11.88 vs. C 16.15 ± 2.58, p < 0.05). The CD42b+ cell population with a role in cell adhesion, and metastasis had a significantly increased value in PCa cases (38.39 ± 11.23) reported to controls (C 26.24 ± 0.62, p < 0.01). The intratumoral expression of CD34 showed a significantly increased pattern of PCa tissue samples reported to controls (PCa 26.12 ± 6.84 vs. C 1.50 ± 0.70, p < 0.01). Flow cytometric analysis of the cell cycle, apoptosis, and adhesion glycoproteins with a critical role in tumoral cell proliferation, T cell infiltrations, Ki-67, and CD 34 expressions by IHC methods are recommended as techniques for the efficient means of measurement for adenocarcinoma and hyperplasia prostate tissue samples and should be explored in the future.
34
Qu, Yunyun, Xin Liu, Shuai Zong, Huanxin Sun, Shuang Liu та Yueran Zhao. "Protocatechualdehyde Inhibits the Osteoclast Differentiation of RAW264.7 and BMM Cells by Regulating NF-κB and MAPK Activity". BioMed Research International 2021 (16 липня 2021): 1–11. http://dx.doi.org/10.1155/2021/6108999.
Повний текст джерелаАнотація:
Protocatechualdehyde (PCA), an important component of Salvia miltiorrhiza, has many activities, such as anti-inflammatory and antisepsis activities. However, the role of PCA in osteoclasts is not clear. We used RAW264.7 cells (a mouse leukemic monocyte/macrophage cell line) and bone marrow macrophages (BMMs) to probe the role of PCA in osteoclasts and the underlying mechanism. The effects of PCA on cell activity were evaluated with CCK-8 assays. TRAP staining detected mature osteoclasts. Corning Osteo Assay Surface plates were used to examine absorption. The levels of RNA and protein were analyzed, respectively, using RT-PCR and Western blotting. PCA (5 μg/ml) was not toxic to the two cell types but reduced the formation of osteoclasts and bone absorption. Furthermore, PCA restrained the expression of mRNAs encoding proteins associated with osteoclasts and reduced the phosphorylation of proteins in important signaling pathways. The results indicate that PCA inhibits osteoclast differentiation by suppressing NF-κB and MAPK activity.
35
Ishii, Kenichiro, Takeshi Sasaki, Kazuhiro Iguchi, Manabu Kato, Hideki Kanda, Yoshifumi Hirokawa, Kiminobu Arima, Masatoshi Watanabe, and Yoshiki Sugimura. "Pirfenidone, an Anti-Fibrotic Drug, Suppresses the Growth of Human Prostate Cancer Cells by Inducing G1 Cell Cycle Arrest." Journal of Clinical Medicine 8, no. 1 (January 4, 2019): 44. http://dx.doi.org/10.3390/jcm8010044.
Повний текст джерелаАнотація:
Pirfenidone (PFD) is an anti-fibrotic drug used to treat idiopathic pulmonary fibrosis by inducing G1 cell cycle arrest in fibroblasts. We hypothesize that PFD can induce G1 cell cycle arrest in different types of cells, including cancer cells. To investigate the effects of PFD treatment on the growth of human prostate cancer (PCa) cells, we used an androgen-sensitive human PCa cell line (LNCaP) and its sublines (androgen-low-sensitive E9 and F10 cells and androgen-insensitive AIDL cells), as well as an androgen-insensitive human PCa cell line (PC-3). PFD treatment suppressed the growth of all PCa cells. Transforming growth factor β1 secretion was significantly increased in PFD-treated PCa cells. In both LNCaP and PC-3 cells, PFD treatment increased the population of cells in the G0/G1 phase, which was accompanied by a decrease in the S/G2 cell population. CDK2 protein expression was clearly decreased in PFD-treated LNCaP and PC-3 cells, whereas p21 protein expression was increased in only PFD-treated LNCaP cells. In conclusion, PFD may serve as a novel therapeutic drug that induces G1 cell cycle arrest in human PCa cells independently of androgen sensitivity. Thus, in the tumor microenvironment, PFD might target not only fibroblasts, but also heterogeneous PCa cells of varying androgen-sensitivity levels.
36
Noble, Amanda R., Karen Hogg, Rakesh Suman, Daniel M. Berney, Sylvain Bourgoin, Norman J. Maitland, and Martin G. Rumsby. "Phospholipase D2 in prostate cancer: protein expression changes with Gleason score." British Journal of Cancer 121, no. 12 (November 1, 2019): 1016–26. http://dx.doi.org/10.1038/s41416-019-0610-7.
Повний текст джерелаАнотація:
Abstract Background Phospholipases D1 and D2 (PLD1/2) are implicated in tumorigenesis through their generation of the signalling lipid phosphatidic acid and its downstream effects. Inhibition of PLD1 blocks prostate cell growth and colony formation. Here a role for PLD2 in prostate cancer (PCa), the major cancer of men in the western world, is examined. Methods PLD2 expression was analysed by immunohistochemistry and western blotting. The effects of PLD2 inhibition on PCa cell viability and cell motility were measured using MTS, colony forming and wound-healing assays. Results PLD2 protein is expressed about equally in luminal and basal prostate epithelial cells. In cells from different Gleason-scored PCa tissue PLD2 protein expression is generally higher than in non-tumorigenic cells and increases in PCa tissue scored Gleason 6–8. PLD2 protein is detected in the cytosol and nucleus and had a punctate appearance. In BPH tissue stromal cells as well as basal and luminal cells express PLD2. PLD2 protein co-expresses with chromogranin A in castrate-resistant PCa tissue. PLD2 inhibition reduces PCa cell viability, colony forming ability and directional cell movement. Conclusions PLD2 expression correlates with increasing Gleason score to GS8. PLD2 inhibition has the potential to reduce PCa progression.
37
Koh, Yoko, Matias A. Bustos, Jamie Moon, Rebecca Gross, Romela Irene Ramos, Suyeon Ryu, Jane Choe, et al. "Urine Cell-Free MicroRNAs in Localized Prostate Cancer Patients." Cancers 14, no. 10 (May 12, 2022): 2388. http://dx.doi.org/10.3390/cancers14102388.
Повний текст джерелаАнотація:
Prostate cancer (PCa) is the most common cancer in men. Prostate-specific antigen screening is recommended for the detection of PCa. However, its specificity is limited. Thus, there is a need to find more reliable biomarkers that allow non-invasive screening for early-stage PCa. This study aims to explore urine microRNAs (miRs) as diagnostic biomarkers for PCa. We assessed cell-free miR (cfmiR) profiles of urine and plasma samples from pre- and post-operative PCa patients (n = 11) and normal healthy donors (16 urine and 24 plasma) using HTG EdgeSeq miRNA Whole Transcriptome Assay based on next-generation sequencing. Furthermore, tumor-related miRs were detected in formalin-fixed paraffin-embedded tumor tissues obtained from patients with localized PCa. Specific cfmiRs signatures were found in urine samples of localized PCa patients using differential expression analysis. Forty-two cfmiRs that were detected were common to urine, plasma, and tumor samples. These urine cfmiRs may have potential utility in diagnosing early-stage PCa and complementing or improving currently available PCa screening assays. Future studies may validate the findings.
38
Yang, Ning, Jiawen Wu, Tiancheng Zhang, Fan Yang, Jinyan Shao, Chang He, and Liang Qin. "Clinical Evaluation of FOXO1 as a Tumor Suppressor in Prostate Cancer." Computational and Mathematical Methods in Medicine 2021 (September 13, 2021): 1–8. http://dx.doi.org/10.1155/2021/8773423.
Повний текст джерелаАнотація:
Objective. Prostate cancer (PCa) is considered the most serious cancer in the world. Nevertheless, the accuracy of current biomarkers, such as pathological staging, Gleason’s score, and serum prostate-specific antigen (PSA) levels, is limited. FOXO1 is a key downstream effector of PTEN and a tumor suppressor in PCA, which has been reported extensively. However, the clinical relevance of FOXO1 in PCa remains unclear. Methods. In this study, we first detected its expression in four public databases to explore the clinical role of FOXO1. Verification of the knockdown effect of FOXO1 siRNA was performed by real-time PCR analysis. Changes in cell viability were assessed using cell counting kit-8 (CCK-8) assays. In addition, we verified the effect of FOXO1 on the PCa cell cycle using a cell cycle assay. Results. Herein, we found that FOXO1 was significantly downregulated in PCa tissues and was significantly associated with Gleason’s score, age, biochemical recurrence (BCR), and lymph node (LN) status, while FOXO1 expression was independent of pathological staging and preoperative PSA levels. The Kaplan-Meier survival analysis showed that PCA patients with high FOXO1 expression were less likely to develop BCR compared with patients with low FOXO1 expression. In terms of function, FOXO1 inhibition significantly promoted the proliferation and cell cycle progression of PCa cells. Conclusions. In summary, our study suggests that FOXO1 may be one of the prognostic factors that describe the risk of PCa for BCR. These results suggest that FOXO1 may be a therapeutic target for PCa.
39
Yu, Kai-Jie, De-Yi Ji, Ming-Li Hsieh, Cheng-Keng Chuang, See-Tong Pang, and Wen-Hui Weng. "EPA Modulates KLK Genes via miR-378: A Potential Therapy in Prostate Cancer." Cancers 14, no. 11 (June 6, 2022): 2813. http://dx.doi.org/10.3390/cancers14112813.
Повний текст джерелаАнотація:
It is known that miRNA-378a-3p (miR-378) could be induced by eicosapentaenoic acid (EPA), an omega-3 fatty acid. Herein, we first demonstrated how miR-378 exerts anti-prostate cancer (PCa) actions by influencing multiple target genes, including KLK2, KLK4, KLK6, and KLK14, which are implicated in PCa development, cell proliferation, and cell survival. Furthermore, these genes also correlate with androgen and mTOR signaling transduction, and are considered pivotal pathways for the onset and progression of PCa. In total, four PCa cell lines and eight pairing tissues (tumor vs. normal) from clinical PCa patients were included in the current study. The results showed high significance after EPA induced tumor cells containing higher expression levels of miR-378, and led the PCa cells having low cell viabilities, and they progressed to apoptosis when compared with normal prostate cells (p < 0.001). The findings indicated that EPA might become a potential therapy for PCa, especially because it is derived from the components of natural fish oil; it may prove to be a great help for solving the problem of castration-resistant prostate cancer (CRPC).
40
Adekoya, Timothy O., Nikia Smith, Ariel J. Thomas, Tonya S. Lane, Nija Burnette, Elizabeth J. Rivers, Yahui Li, Xiaoxin L. Chen та Ricardo M. Richardson. "Host versus cell-dependent effects of β-arrestin 1 expression in prostate tumorigenesis". Carcinogenesis 42, № 5 (12 березня 2021): 772–83. http://dx.doi.org/10.1093/carcin/bgab021.
Повний текст джерелаАнотація:
Abstract Prostate cancer (PCa) constitutes a serious health challenge and remains one of the main causes of cancer-related death among men. The more aggressive form of the disease has been attributed to androgen independence, resulting in a lack of response to androgen deprivation therapy and sustained activation of other growth pathways. The scaffold proteins β-arrestin 1 and 2 (βarr1 and βarr2), which are known to mediate G protein-coupled receptor desensitization and internalization, were also shown to modulate prostate tumorigenesis. βarr1 is significantly overexpressed (>4-fold) in PCa cells relative to βarr2. In this study, we investigated the effect of βarr1 overexpression in PCa development and progression using the mouse and human PCa cell xenografts, and autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) models deficient in β-arrestin depletion of βarr1 in TRAMP mice (TRAMP/βarr1−/−) increased PCa growth and decreased overall survival relative to control TRAMP or TRAMP/βarr2−/− animals. Prostate tissues from TRAMP/βarr1−/− tumors displayed an increase in androgen receptor (AR) expression, whereas overexpression of βarr1 in TRAMP-C1 (TRAMP-C1-βarr1-GFP) which derived from TRAMP decreased AR expression, cell proliferation and tumor growth in nude mice xenografts, relative to control TRAMP-C1-GFP. Knockdown of βarr1 expression in human MDA PCa 2b cells (MDA PCa 2b-βarr1−/−) also decreased AR expression cell proliferation and tumor growth relative to control (MDA PCa 2b-Sham) cells. Interestingly, both TRAMP-C1-βarr1-GFP and MDA PCa 2b-βarr1−/− xenografts showed a decrease in AKT phosphorylation but an increase in MAPK activation. Altogether, the data indicate that the effect of βarr1 in modulating AR signaling to regulate PCa aggressiveness is cell and host autonomous.
41
Bian, Xiaojie, Wenfeng Wang, Mierxiati Abudurexiti, Zhu Yao, Min Zhang, Ding-Wei Ye, and Jianhua Wang. "Integration analysis of single-cell multi-omics in the prostate cancer ecosystem." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): e17046-e17046. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e17046.
Повний текст джерелаАнотація:
e17046 Background: Prostate cancer (PCa) is characterized as a extensive heterogeneous disease with the complex cellular ecosystem in the tumor microenvironment (TME). However, the content of how heterogeneity is shaped by tumors and stromal cells or vice versa remains poorly understood. Methods: Single-cell RNA sequencing, spatial transcriptomics and bulk ATAC-sequence from a series of human PCa and normal control were integrated. Results: We identified a stemness subset of club cells marked with SOX9highARlow expression, which enriched significantly after neoadjuvant androgen-deprivation therapy (ADT). Furthermore, a subset of CD8+CXCR6+ T cell, functioned as effector T cell, was observed to be markedly reduced in the malignant PCa patients. Notably, immunosuppressive microenvironment in advanced PCa was associated with infiltration of regulatory T cells (Tregs), which is potentially induced by FAP+ fibroblasts (cancer-associated fibroblasts, CAFs subset). Moreover, for spatial transcriptome analysis, we comprehensively utilized machine learning and computational intelligence to identify cellular diversity of prostate and cell-cell communication with each other in situ.Importantly, we also depicted macrophage and neutrophil state transition under different biological conditions in vivo. Conclusions: We delineate the cellular heterogeneity in the stage-specific PCa microenvironment at single-cell resolution, uncover their reciprocal crosstalk with disease progression and these results will be helpful in exploring potential target for PCa therapy.
42
Erb, Holger H. H., Regina V. Langlechner, Patrizia L. Moser, Florian Handle, Tineke Casneuf, Karin Verstraeten, Bettina Schlick та ін. "IL6 sensitizes prostate cancer to the antiproliferative effect of IFNα2 through IRF9". Endocrine-Related Cancer 20, № 5 (2 серпня 2013): 677–89. http://dx.doi.org/10.1530/erc-13-0222.
Повний текст джерелаАнотація:
Development and progression of prostate cancer (PCa) are associated with chronic inflammation. The cytokine interleukin 6 (IL6) can influence progression, differentiation, survival, and angiogenesis of PCa. To identify novel pathways that are triggered by IL6, we performed a gene expression profiling of two PCa cell lines, LNCaP and MDA PCa 2b, treated with 5 ng/ml IL6. Interferon (IFN) regulatory factor 9 (IRF9) was identified as one of the most prevalent IL6-regulated genes in both cell lines. IRF9 is a mediator of type I IFN signaling and acts together with STAT1 and 2 to activate transcription of IFN-responsive genes. The IL6 regulation of IRF9 was confirmed at mRNA and protein levels by quantitative real-time PCR and western blot respectively in both cell lines and could be blocked by the anti-IL6 antibody Siltuximab. Three PCa cell lines, PC3, Du-145, and LNCaP-IL6+, with an autocrine IL6 loop displayed high expression of IRF9. A tissue microarray with 36 PCa tissues showed that IRF9 protein expression is moderately elevated in malignant areas and positively correlates with the tissue expression of IL6. Downregulation and overexpression of IRF9 provided evidence for an IFN-independent role of IRF9 in cellular proliferation of different PCa cell lines. Furthermore, expression of IRF9 was essential to mediate the antiproliferative effects of IFNα2. We concluded that IL6 is an inducer of IRF9 expression in PCa and a sensitizer for the antiproliferative effects of IFNα2.
43
Méndez Palacios, Néstor, María Elena Ayala Escobar, Maximino Méndez Mendoza, Rubén Huerta Crispín, Octavio Guerrero Andrade, Javier Hernández Melández, and Andrés Aragón Martínez. "Prepubertal male rats with high rates of germ-cell apoptosis present exacerbated rates of germ-cell apoptosis after serotonin depletion." Reproduction, Fertility and Development 28, no. 6 (2016): 806. http://dx.doi.org/10.1071/rd13382.
Повний текст джерелаАнотація:
Male germ-cell apoptosis occurs naturally and can be increased by exposure to drugs and toxic chemicals. Individuals may have different rates of apoptosis and are likely to also exhibit differential sensitivity to outside influences. Previously, we reported that p-chloroamphetamine (pCA), a substance that inhibits serotonin synthesis, induced germ-cell apoptosis in prepubertal male rats. Here, we identified prepubertal rats with naturally high or low rates of germ-cell apoptosis and evaluated gene expression in both groups. Bax and Shbg mRNA levels were higher in rats with high rates of germ-cell apoptosis. Rats were then treated with pCA and the neuro-hormonal response and gene expression were evaluated. Treatment with pCA induced a reduction in serotonin concentrations but levels of sex hormones and gonadotrophins were not changed. Rats with initially high rates of germ-cell apoptosis had even higher rates of germ-cell apoptosis after treatment with pCA. In rats with high rates of germ-cell apoptosis Bax mRNA expression remained high after treatment with pCA. On the basis of category, an inverse relationship between mRNA expression of Bax and Bcl2, Bax and AR and Bax and Hsd3b2 was found. Here we provide evidence that innate levels of germ-cell apoptosis could be explained by the level of mRNA expression of genes involved with apoptosis and spermatogenesis.
44
Bacci, Lorenza, Aurora Aiello, Cristian Ripoli, Rossella Loria, Dario Pugliese, Francesco Pierconti, Dante Rotili та ін. "H19-Dependent Transcriptional Regulation of β3 and β4 Integrins Upon Estrogen and Hypoxia Favors Metastatic Potential in Prostate Cancer". International Journal of Molecular Sciences 20, № 16 (17 серпня 2019): 4012. http://dx.doi.org/10.3390/ijms20164012.
Повний текст джерелаАнотація:
Estrogen and hypoxia promote an aggressive phenotype in prostate cancer (PCa), driving transcription of progression-associated genes. Here, we molecularly dissect the contribution of long non-coding RNA H19 to PCa metastatic potential under combined stimuli, a topic largely uncovered. The effects of estrogen and hypoxia on H19 and cell adhesion molecules’ expression were investigated in PCa cells and PCa-derived organotypic slice cultures (OSCs) by qPCR and Western blot. The molecular mechanism was addressed by chromatin immunoprecipitations, overexpression, and silencing assays. PCa cells’ metastatic potential was analyzed by in vitro cell-cell adhesion, motility test, and trans-well invasion assay. We found that combined treatment caused a significant H19 down-regulation as compared with hypoxia. In turn, H19 acts as a transcriptional repressor of cell adhesion molecules, as revealed by up-regulation of both β3 and β4 integrins and E-cadherin upon H19 silencing or combined treatment. Importantly, H19 down-regulation and β integrins induction were also observed in treated OSCs. Combined treatment increased both cell motility and invasion of PCa cells. Lastly, reduction of β integrins and invasion was achieved through epigenetic modulation of H19-dependent transcription. Our study revealed that estrogen and hypoxia transcriptionally regulate, via H19, cell adhesion molecules redirecting metastatic dissemination from EMT to a β integrin-mediated invasion.
45
Chen, Zheng, Tao Qi, Xiao-ping Qin, Jue Wang, Zhang-sen Huang, Xiao-yong Hu, Guo Chen, Li-jun Qu, and Yu-min Zhuo. "Long Noncoding RNA SNHG12 Promotes Prostate Tumor Occurrence and Progression via AKT Regulation." BioMed Research International 2020 (December 22, 2020): 1–11. http://dx.doi.org/10.1155/2020/8812923.
Повний текст джерелаАнотація:
The small nucleolar RNA host gene 12 (SNHG12) has been reported to play an important role in the tumorigenesis and progression of PCa, but the functional underlying mechanism has not been studied clearly. We detected the expression level of SNHG12 in PCa tissues and matched adjacent normal tissues that were collected from 85 patients. Then, colony formation assays, MTT experiments, and flow cytometry were used to examine the effect of SNHG12 on proliferation, cell cycle distribution, and apoptosis of DU145 cells. Further, Transwell invasion assay was utilized to assess whether SNHG12 participates in PCa cell invasion and affects the secretion of VEGF secretion in DU145 cells. Finally, we investigated the effect of SNHG12 on tumor growth in vivo. We found that SNHG12 promoted cell proliferation and suppressed apoptosis in PCa cells, which suggests that SNHG12 is probably a novel PCa biomarker and therapy target of PCa.
46
Namekawa, Takeshi, Kazuhiro Ikeda, Kuniko Horie-Inoue, and Satoshi Inoue. "Application of Prostate Cancer Models for Preclinical Study: Advantages and Limitations of Cell Lines, Patient-Derived Xenografts, and Three-Dimensional Culture of Patient-Derived Cells." Cells 8, no. 1 (January 20, 2019): 74. http://dx.doi.org/10.3390/cells8010074.
Повний текст джерелаАнотація:
Various preclinical models have been developed to clarify the pathophysiology of prostate cancer (PCa). Traditional PCa cell lines from clinical metastatic lesions, as exemplified by DU-145, PC-3, and LNCaP cells, are useful tools to define mechanisms underlying tumorigenesis and drug resistance. Cell line-based experiments, however, have limitations for preclinical studies because those cells are basically adapted to 2-dimensional monolayer culture conditions, in which the majority of primary PCa cells cannot survive. Recent tissue engineering enables generation of PCa patient-derived xenografts (PDXs) from both primary and metastatic lesions. Compared with fresh PCa tissue transplantation in athymic mice, co-injection of PCa tissues with extracellular matrix in highly immunodeficient mice has remarkably improved the success rate of PDX generation. PDX models have advantages to appropriately recapitulate the molecular diversity, cellular heterogeneity, and histology of original patient tumors. In contrast to PDX models, patient-derived organoid and spheroid PCa models in 3-dimensional culture are more feasible tools for in vitro studies for retaining the characteristics of patient tumors. In this article, we review PCa preclinical model cell lines and their sublines, PDXs, and patient-derived organoid and spheroid models. These PCa models will be applied to the development of new strategies for cancer precision medicine.
47
Sun, Xin-bo, Yong-wei Chen, Qi-sheng Yao, Xu-hua Chen, Min He, Cong-bo Chen, Yong Yang, Xiao-xin Gong, and Li Huang. "MicroRNA-144 Suppresses Prostate Cancer Growth and Metastasis by Targeting EZH2." Technology in Cancer Research & Treatment 20 (January 1, 2021): 153303382198981. http://dx.doi.org/10.1177/1533033821989817.
Повний текст джерелаАнотація:
Background: Prostate cancer is a common malignant tumor with a high incidence. MicroRNAs (miRNAs) have been shown to be important post-transcriptional regulators during tumorigenesis. This study aimed to explore the effect of miR-144 on PCa proliferation and apoptosis. Material and Methods: The expression of miR-144 and EZH2 were examined in clinical PCa tissues. PCa cell line LNCAP and DU-145 was employed and transfected with miR-144 mimics or inhibitors. The correlation between miR-144 and EZH2 was verified by luciferase reporter assay. Cell viability, apoptosis and migratory capacity were detected by CCK-8, flow cytometry assay and wound healing assay. The protein level of EZH2, E-Cadherin, N-Cadherin and vimentin were analyzed by western blotting. Results: miR-144 was found to be negatively correlated to the expression of EZH2 in PCa tissues. Further studies identified EZH2 as a direct target of miR-144. Moreover, overexpression of miR-144 downregulated expression of EZH2, reduced cell viability and promoted cell apoptosis, while knockdown of miR-144 led to an inverse result. miR-144 also suppressed epithelial-mesenchymal transition level of PCa cells. Conclusion: Our study indicated that miR-144 negatively regulate the expression of EZH2 in clinical specimens and in vitro. miR-144 can inhibit cell proliferation and induce cell apoptosis in PCa cells. Therefore, miR-144 has the potential to be used as a biomarker for predicting the progression of PCa.
48
Garofano, Kaitlin, Kameron Rashid, Michael Smith, Christine Brantner, Sumanun Suwunnakorn, David Diemert, Olivia Gordon, et al. "Prostate cancer cell-platelet bidirectional signaling promotes calcium mobilization, invasion and apoptotic resistance via distinct receptor-ligand pairs." Scientific Reports 13, no. 1 (February 17, 2023). http://dx.doi.org/10.1038/s41598-023-29450-x.
Повний текст джерелаАнотація:
AbstractPlatelets play a crucial role in cancer and thrombosis. However, the receptor-ligand repertoire mediating prostate cancer (PCa) cell-platelet interactions and ensuing consequences have not been fully elucidated. Microvilli emanating from the plasma membrane of PCa cell lines (RC77 T/E, MDA PCa 2b) directly contacted individual platelets and platelet aggregates. PCa cell-platelet interactions were associated with calcium mobilization in platelets, and translocation of P-selectin and integrin αIIbβ3 onto the platelet surface. PCa cell-platelet interactions reciprocally promoted PCa cell invasion and apoptotic resistance, and these events were insensitive to androgen receptor blockade by bicalutamide. PCa cells were exceedingly sensitive to activation by platelets in vitro, occurring at a PCa cell:platelet coculture ratio as low as 1:10 (whereas PCa patient blood contains 1:2,000,000 per ml). Conditioned medium from cocultures stimulated PCa cell invasion but not apoptotic resistance nor platelet aggregation. Candidate transmembrane signaling proteins responsible for PCa cell-platelet oncogenic events were identified by RNA-Seq and broadly divided into 4 major categories: (1) integrin-ligand, (2) EPH receptor-ephrin, (3) immune checkpoint receptor-ligand, and (4) miscellaneous receptor-ligand interactions. Based on antibody neutralization and small molecule inhibitor assays, PCa cell-stimulated calcium mobilization in platelets was found to be mediated by a fibronectin1 (FN1)-αIIbβ3 signaling axis. Platelet-stimulated PCa cell invasion was facilitated by a CD55-adhesion G protein coupled receptor E5 (ADGRE5) axis, with contribution from platelet cytokines CCL3L1 and IL32. Platelet-stimulated PCa cell apoptotic resistance relied on ephrin-EPH receptor and lysophosphatidic acid (LPA)-LPA receptor (LPAR) signaling. Of participating signaling partners, FN1 and LPAR3 overexpression was observed in PCa specimens compared to normal prostate, while high expression of CCR1 (CCL3L1 receptor), EPHA1 and LPAR5 in PCa was associated with poor patient survival. These findings emphasize that non-overlapping receptor-ligand pairs participate in oncogenesis and thrombosis, highlighting the complexity of any contemplated clinical intervention strategy.
49
Abdullah, K. M., Gunjan Sharma, Simran Takkar, Jyoti B. Kaushal, Ramesh Pothuraju, Bandana Chakravarti, Surinder K. Batra та Jawed A. Siddiqui. "α-lipoic acid modulates prostate cancer cell growth and bone cell differentiation". Scientific Reports 14, № 1 (22 лютого 2024). http://dx.doi.org/10.1038/s41598-024-54479-x.
Повний текст джерелаАнотація:
AbstractProstate cancer (PCa) progression leads to bone modulation in approximately 70% of affected men. A nutraceutical, namely, α-lipoic acid (α-LA), is known for its potent anti-cancer properties towards various cancers and has been implicated in treating and promoting bone health. Our study aimed to explore the molecular mechanism behind the role of α-LA as therapeutics in preventing PCa and its associated bone modulation. Notably, α-LA treatment significantly reduced the cell viability, migration, and invasion of PCa cell lines in a dose-dependent manner. In addition, α-LA supplementation dramatically increased reactive oxygen species (ROS) levels and HIF-1α expression, which started the downstream molecular cascade and activated JNK/caspase-3 signaling pathway. Flow cytometry data revealed the arrest of the cell cycle in the S-phase, which has led to apoptosis of PCa cells. Furthermore, the results of ALP (Alkaline phosphatase) and TRAP (tartrate-resistant acid phosphatase) staining signifies that α-LA supplementation diminished the PCa-mediated differentiation of osteoblasts and osteoclasts, respectively, in the MC3T3-E1 and bone marrow macrophages (BMMs) cells. In summary, α-LA supplementation enhanced cellular apoptosis via increased ROS levels, HIF-1α expression, and JNK/caspase-3 signaling pathway in advanced human PCa cell lines. Also, the treatment of α-LA improved bone health by reducing PCa-mediated bone cell modulation.
50
Liao, Jinling, Qiong Song, Jie Li, Kechen Du, Yang Chen, Chunlin Zou, and Zengnan Mo. "Carcinogenic effect of adenylosuccinate lyase (ADSL) in prostate cancer development and progression through the cell cycle pathway." Cancer Cell International 21, no. 1 (September 6, 2021). http://dx.doi.org/10.1186/s12935-021-02174-6.
Повний текст джерелаАнотація:
Abstract Background Prostate cancer (PCa) is still a serious male malignant disease across the world. However, no exact pathogenesis had been explained. Although adenylosuccinate lyase (ADSL) gene was identified to be important in PCa early in 1987, its comprehensive functions for PCa have not been presented. Methods The cBioPortal for Cancer Genomics, Oncomine and GEO database were retrieved to investigate the associations between of the ADSL gene and PCa. Then, the PC-3, DU145 and C4-2B cell lines were applied in vitro experiments. RNA sequencing and further western blot (WB) were applied to explore the potential mechanisms of ADSL gene in PCa. Results Based on PCa clinical datasets, we firstly found ADSL gene highly expressed in PCa tissues. Moreover, its transcript level increased in the metastatic PCa further. Elevated ADSL gene expression indicated a poor prognosis of PCa. While inhibiting the expression of ADSL with siRNA, the ability of cell proliferation and migration all declined markedly, with increased cell apoptosis inversely. Most of cells were blocked in the G0/G1 phase. Additionally, RNA sequencing also discovered the inactivity of cell cycle pathway after ADSL knockdown, which had also confirmed on the proteins levels. Conclusions Our study identified the ADSL as an oncogene of PCa through regulating the cell cycle pathway firstly, with explicit cell and clinical phenotypes. Further mechanisms were needed to confirm its carcinogenic effect.