Micro-ribonucleic acid 29b inhibits cell proliferation and invasion and enhances cell apoptosis and chemotherapy effects of cisplatin via targeting of DNMT3b and AKT3 in prostate cancer

Abstract

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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