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Long non-coding RNAs (lncRNAs) are involved in the pathogenesis of prostate cancer (PCa) as competitive endogenous RNA. The present study aimed to investigate the molecular mechanisms of lncRNA small nucleolar RNA host gene 16 (SNHG16) in the proliferation and metastasis of PCa cells. Cancer tissues and adjacent normal tissues were collected from 80 patients with PCa who did not receive any treatment. Reverse transcription-quantitative PCR analysis was performed to detect the expression levels of SNHG16, hsa-microRNA (miRNA/miR)-373-3p and transforming growth factor-β receptor type 2 (TGF-β-R2), and Spearman's correlation coefficient analysis was performed to assess the correlations between these molecules. Furthermore, the effects of SNHG16 knockdown and overexpression on the biological functions of DU-145 PCa cells and TGF-β-R2/SMAD signaling were analyzed. The dual-luciferase reporter assay was performed to assess the associations between SNHG16 and miR-373-3p, and TGF-β-R2 and miR-373-3p, the effects of which were verified via rescue experiments. The results demonstrated that the expression levels of SNHG16 and TGF-β-R2 were significantly upregulated in PCa tissues, whereas miR-373-3p expression was significantly downregulated (P<0.001). In addition, negative correlations were observed between SNHG16 and miR-373-3p (rho, −0.631) and miR-373-3p and TGF-β-R2 (rho, −0.516). Overexpression of SNHG16 significantly promoted the proliferation, migration and invasion of PCa cells (P<0.05), and significantly increased the protein expression levels of TGF-β-R2, phosphorylated (p)-SMAD2, p-SMAD3, c-Myc and E2F4 (P<0.001). Notably, the results revealed that miR-373-3p is a target of SNHG16, and miR-373-3p knockdown rescued short hairpin (sh)-SNHG16-suppressed cellular functions by promoting TGF-β-R2/SMAD signaling. The results also revealed that miR-373-3p targets TGF-β-R2. Notably, transfection with miR-373-3p inhibitor rescued sh-TGF-β-R2-suppressed cell proliferation and migration. Taken together, the results of the present study suggest that SNHG16 promotes the proliferation and migration of PCa cells by targeting the miR-373-3p/TGF-β-R2/SMAD axis. [ABSTRACT FROM AUTHOR]

Previous studies have reported that the expression levels of microRNA (miR)-28-3p are downregulated in prostate cancer (PCa) compared with those in adjacent normal tissues. However, to the best of our knowledge, the function and underlying mechanisms of miR-28-3p in PCa have not been reported. The present study aimed to explore the role of miR-28-3p and its mechanism in the development of PCa. In the present study, miR-28-3p and ADP-ribosylation factor 6 (ARF6) expression levels were analyzed using reverse transcription-quantitative PCR (RT-qPCR). Cell proliferation, colony formation, apoptosis, migration and invasion were determined using Cell Counting Kit-8, colony forming, flow cytometry and Transwell assays, respectively. The association between miR-28-3p and ARF6 was investigated using a dual luciferase reporter assay. ARF6, Rac1, Erk1/2 and phosphorylated (p)-Erk1/2 protein expression levels were analyzed using western blotting. The results of the present study revealed that miR-28-3p expression levels were downregulated, whereas ARF6 expression levels were upregulated in PCa cell lines (LNCaP, 22Rv-1, PC-3 and DU145) compared with those in the normal prostate line RWPE-1. The overexpression of miR-28-3p promoted cell apoptosis, and inhibited cell proliferation, colony formation, migration and invasion. However, the knockdown of miR-28-3p exerted the opposite results. The results of the dual luciferase reporter assays, RT-qPCR and western blotting indicated that ARF6 was a target gene of miR-28-3p. Finally, rescue experiments demonstrated that ARF6 overexpression attenuated the effects of the miR-28-3p mimic by upregulating Rac1 and p-Erk1/2 expression in PCa cells. In conclusion, these findings indicated that miR-28-3p may inhibit the biological behaviors of PCa cells by targeting ARF6, and therefore may represent a novel therapeutic candidate for PCa. [ABSTRACT FROM AUTHOR]