MicroRNAs (miRNAs) present frequently altered expression in urologic cancers including prostate, bladder, and kidney cancer. The altered expression of miR-223 has been reported in cancers and other diseases in recent researches. MiR-223 is up-regulated in systemic lupus erythematosus and rheumatoid arthritis. In neoplastic diseases, miR-223 is proved to be up-expressed in plasma or serum and cancer tissues compared with normal tissues in pancreatic cancer, gastric cancer, et al. However, whether altered expression of miR-223 is associated with prostate cancer (PCa) and what it is potential functions in PCa remained unveiled. In this study, we firstly found miR-223-3p were up-regulated in prostate cancer tissues and then we study functional role of miR-223-3p in PCa using DU145, PC3 and LNCaP cell lines. Our data suggested that miR-223-3p might target gene SEPT6 and promoted the biological behavior of prostate cancer. Notably, we found increasing SEPT6 expression might reverse the biological activity induced by miR-223-3p, which might be a potential therapeutic target for PCa.
BackgroundMicro-ribonucleic acids (miRNAs) are crucial regulators in malignant tumors. miRNA-29b (miR-29b) has been identified as a tumor suppressor in prostate cancer (PCa). However, very few studies have investigated the effects of miR-29b in PCa, especially the mechanism and its association with chemotherapy. Our study aimed to explore the role and mechanism of miR-29b in PCa.Materials and methodsThe expression levels of miR-29b were detected in ten clinical PCa specimens and four different PCa cell lines through quantitative real-time polymerase chain reaction. After miR-29b mimics and inhibitors were successfully transfected into LNCaP, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was then used to investigate cell proliferation and cisplatin sensitivity of PCa cells. Cell cycle, cell apoptosis, and cell invasion were detected via flow cytometry, annexin V–fluorescein isothiocyanate labeling, and transwell assay, respectively. Based on bioinformatic methods, Western blot analysis, and dual-luciferase reporter assay, novel target genes of miR-29b were identified.ResultsmiR-29b was downregulated in PCa tissues compared with matched adjacent nontumor tissues. In the androgen-independent PCa cell line (LNCaP-AI), the expression of miR-29b was much lower than the androgen-dependent PCa cell line (LNCaP). Subsequent studies showed that forced expression of miR-29b inhibited cell proliferation and cell invasion and induced cell apoptosis in PCa. Upregulation of miR-29b also enhanced the chemosensitivity of PCa cells to cisplatin. Moreover, we identified DNMT3b and AKT3 as novel target genes of miR-29b in PCa.ConclusionTaken together, the results showed that miR-29b plays a tumor-suppressive role in PCa. It inhibits cell biological behavior and enhances the chemotherapy effects of cisplatin through its involvement in epigenetic regulation and PI3K/AKT pathway.
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