Int J Biol Sci. 2020 Feb 21;16(8):1417-1426.doi: 10.7150/ijbs.42019. eCollection 2020. (IF:10.75).

miR-197-3p Represses the Proliferation of Prostate Cancer by Regulating the VDAC1/AKT/β-catenin Signaling Axis

Affiliations

Affiliations

  • 1 Department of Urology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China.
  • 2 Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China.
  • 3 Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China.

Free PMC article

Abstract

Accumulating investigations have demonstrated that microRNAs (miRNAs) are promising efficient targets for the next generation of molecular therapeutics. The development of miRNA-based therapies requires the identification and validation of cancer-associated miRNAs. Herein, we identified that miR-197-3p regulates the carcinogenesis and development of prostate cancer (PCa) via bioinformatics analysis. Next, we investigated the function and regulatory mechanisms of miR-197-3p in PCa. Overexpression of miR-197-3p suppressed PCa cell proliferation and colony formation. In contrast, inhibition of miR-197-3p activity enhanced PCa cell proliferation and colony formation. Mechanistic investigations identified that voltage dependent anion channel 1 (VDAC1) is a direct target of miR-197-3p. miR-197-3p targeting of VDAC1 resulted in downregulation of p-Akt and β-catenin. Subsequently, we found that restoration of VDAC1 abolished the effects of miR-197-3p on PCa cell proliferation and AKT signaling pathway. Furthermore, we confirmed that miR-197-3p suppressed tumor xenograft growth in vivo. In conclusion, our study offers an empirical investigation of miR-197-3p, a tumor suppressor that may be a potential therapeutic target in PCa.

Keywords: AKT; VDAC1; miR-197-3p; prostate cancer.

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