Tumor-suppressive microRNA-218 inhibits tumor angiogenesis via targeting the mTOR component RICTOR in prostate cancer

Abstract

// Bing Guan 1, * , Kaijie Wu 1, 2, * , Jin Zeng 1, 2 , Shan Xu 1, 2 , Lijun Mu 1 , Yang Gao 1 , Ke Wang 1, 2 , Zhenkun Ma 1, 2 , Juanhua Tian 1 , Qi Shi 1 , Peng Guo 1, 2 , Xinyang Wang 1, 2 , Dalin He 1, 2 , Yuefeng Du 1, 2 1 Department of Urology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China 2 Oncology Research Laboratory, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an, Shaanxi, China * These authors have contributed equally to this work Correspondence to: Dalin He, email: dalinhexjtu@163.com Yuefeng Du, email: duyuefeng113@163.com Keywords: microRNA-218, prostate cancer, angiogenesis, VEGFA, RICTOR Received: May 09, 2016     Accepted: November 01, 2016     Published: December 24, 2016 ABSTRACT MicroRNAs, a kind of small non-coding RNAs, can regulate gene expression by targeting mRNAs for translational repression or degradation. Much evidence has suggested that miR-218 was a tumor suppressor in many human cancers including prostate cancer. However, the underlying role of miR-218 in tumor angiogenesis and the mechanisms in PCa and other cancers remains to be unclear. Here in this present study, we demonstrated that miR-218 inhibited the tumor angiogenesis of PCa cells in vitro and in vivo. RICTOR, the mTOR component 2, was a direct target of miR-218 and miR218-RICTOR-VEGFA axis was the mechanism inhibiting the tumor angiogenesis of PCa cells. RICTOR knockdown phenocopied miR-218 overexpression in inhibiting prostate cancer angiogenesis. Altogether, our findings indicate that down-regulation of miR-218 contributes to tumor angiogenesis through RICTOR/VEGFA axis in PCa, providing new insights into the potential mechanisms of PCa oncogenesis and revealing the potential of miR-218 as a useful serum biomarker and a new therapeutic target for human PCa.