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

Bing Guan,Yang Gao,Shan Xu,Dalin He,Peng Guo,Lijun Mu,Kaijie Wu,Yuefeng Du,Zhenkun Ma,Jin Zeng,Xinyang Wang,Ke Wang,Juanhua Tian,Qi Shi

doi:10.18632/oncotarget.14131

Bing Guan, Yang Gao + Show 12 more

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https://doi.org/10.18632/oncotarget.14131

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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.

Highlights

Prostate cancer (PCa) is the second most frequently diagnosed cancer among men worldwide, with estimated 903,500 new cases and 258,400 deaths per year [1]
To determine whether miR-218 is mis-regulated in PCa cell lines, we performed miRNA RT–PCR experiments, and the result showed that several PCa cell lines, including LNCaP, C4-2 and CWR22Rv1, had undetectable or very low level of miR-218 expression compared to normal prostate epithelial cell line BPH-1 (Figure 1A)
The conditioned medium (CM) of these cells was collected, and an in vitro endothelial recruitment assay was used to investigate the effects of miR-218 on the migration of human umbilical vein endothelial cells (HUVECs)

Summary

Introduction

Prostate cancer (PCa) is the second most frequently diagnosed cancer among men worldwide, with estimated 903,500 new cases and 258,400 deaths per year [1]. In the United States, 220,800 new prostate cancer cases and 27,540 cancer deaths are estimated to occur in 2015 [2]. A significant amount of evidence has suggested that miRNAs are aberrantly expressed in many human cancer types and play important roles in the cancer initiation, development and metastasis [6, 7]. MiR-874 suppresses gastric cancer progression by modulating angiogenesis through STAT3/VEGF-A pathway [11]. Published data shows that miR-218 is a tumor suppressive miRNA in human cancers including prostate cancer. The role of miR-218 in PCa angiogenesis remains unknown

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