Guan Bing, Wu Kaijie, Zeng Jin, Xu Shan, Mu Lijun, Gao Yang, Wang Ke, Ma Zhenkun, Tian Juanhua, Shi Qi, Guo Peng, Wang Xinyang, He Dalin, Du Yuefeng
Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Oncology Research Laboratory, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, China.
Oncotarget. 2017 Jan 31;8(5):8162-8172. doi: 10.18632/oncotarget.14131.
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.
微小RNA是一类小的非编码RNA，可通过靶向mRNA进行翻译抑制或降解来调节基因表达。大量证据表明，miR-218在包括前列腺癌在内的许多人类癌症中是一种肿瘤抑制因子。然而，miR-218在肿瘤血管生成中的潜在作用以及在前列腺癌和其他癌症中的机制仍不清楚。在本研究中，我们证明miR-218在体外和体内均抑制前列腺癌细胞的肿瘤血管生成。mTOR组分2 RICTOR是miR-218的直接靶点，miR218-RICTOR-VEGFA轴是抑制前列腺癌细胞肿瘤血管生成的机制。RICTOR基因敲低在抑制前列腺癌血管生成方面模拟了miR-218过表达。总之，我们的研究结果表明，miR-218的下调通过RICTOR/VEGFA轴促进前列腺癌的肿瘤血管生成，为前列腺癌发生的潜在机制提供了新的见解，并揭示了miR-218作为有用的血清生物标志物和人类前列腺癌新治疗靶点的潜力。
