Wenbiao Liao1, Yi Zhang2. 1. Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430000, PR China. 2. Department of Urology, People's Hospital of Hanchuan, Hanchuan 431600, PR China. Electronic address: zyzhangyi2008@126.com.
Abstract
AIM: MicroRNAs (miRNAs) function as oncogenes or tumor suppressors in an extensive variety of human cancers, including prostate cancer (PCa). Herein, the aim of this study is to investigate the effect of miR-381 on autophagy and apoptosis of PCa cells through the reelin (RELN)-mediated the PI3K/AKT/mTOR signaling pathway. METHODS: PCa-related differentially expressed genes and regulatory miRNA were retrieved according to microarray-based analysis and online mRNA-miRNA interaction analysis. The regulatory relationship between miR-381 and RELN was verified by bioinformatics prediction and dual-luciferase reporter gene assay. Gain- and loss-of-function experiments were applied to analyze the effects of miR-381 and RELN on the abilities of proliferation, apoptosis as well as autophagy of PCa cells. Furthermore, xenograft tumor was developed in nude mice to examine the tumorigenic ability of PCa. KEY FINDINGS: RELN, which was found to be up-regulated in PCa, was identified as a target of miR-381. Overexpressed miR-381 suppressed PCa cell proliferation while promoted autophagy and apoptosis of PCa cells. In addition, miR-381 inhibited the activation of the PI3K/AKT/mTOR signaling pathway by targeting RELN. In vivo experiments also confirmed that overexpression of miR-381 could inhibit the tumorigenic ability of PCa. CONCLUSION: Up-regulation of miR-381 inhibits the expression of RELN, which in turn inhibits the activation of the PI3K/AKT/mTOR signaling pathway, thereby inhibiting PCa cell proliferation, and promoting PCa cell apoptosis and autophagy.
AIM: MicroRNAs (miRNAs) function as oncogenes or tumor suppressors in an extensive variety of humancancers, including prostate cancer (PCa). Herein, the aim of this study is to investigate the effect of miR-381 on autophagy and apoptosis of PCa cells through the reelin (RELN)-mediated the PI3K/AKT/mTOR signaling pathway. METHODS:PCa-related differentially expressed genes and regulatory miRNA were retrieved according to microarray-based analysis and online mRNA-miRNA interaction analysis. The regulatory relationship between miR-381 and RELN was verified by bioinformatics prediction and dual-luciferase reporter gene assay. Gain- and loss-of-function experiments were applied to analyze the effects of miR-381 and RELN on the abilities of proliferation, apoptosis as well as autophagy of PCa cells. Furthermore, xenograft tumor was developed in nude mice to examine the tumorigenic ability of PCa. KEY FINDINGS:RELN, which was found to be up-regulated in PCa, was identified as a target of miR-381. Overexpressed miR-381 suppressed PCa cell proliferation while promoted autophagy and apoptosis of PCa cells. In addition, miR-381 inhibited the activation of the PI3K/AKT/mTOR signaling pathway by targeting RELN. In vivo experiments also confirmed that overexpression of miR-381 could inhibit the tumorigenic ability of PCa. CONCLUSION: Up-regulation of miR-381 inhibits the expression of RELN, which in turn inhibits the activation of the PI3K/AKT/mTOR signaling pathway, thereby inhibiting PCa cell proliferation, and promoting PCa cell apoptosis and autophagy.
Authors: Milad Ashrafizadeh; Mahshid Deldar Abad Paskeh; Sepideh Mirzaei; Mohammad Hossein Gholami; Ali Zarrabi; Farid Hashemi; Kiavash Hushmandi; Mehrdad Hashemi; Noushin Nabavi; Francesco Crea; Jun Ren; Daniel J Klionsky; Alan Prem Kumar; Yuzhuo Wang Journal: J Exp Clin Cancer Res Date: 2022-03-22