Tumor-suppressive microRNA-218 inhibits tumor angiogenesis via targeting the mTOR component RICTOR in prostate cancer.
Tumor-suppressive microRNA-218 inhibits tumor angiogenesis via targeting the mTOR component RICTOR in prostate cancer.
复制标题
肿瘤抑制性 microRNA-218 通过靶向前列腺癌中的 mTOR 成分 RICTOR 抑制肿瘤血管生成
DOI：
10.18632/oncotarget.14131
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发表时间：
2017-01-31
期刊：
影响因子：
--
通讯作者：
Du Y
中科院分区：
文献类型：
--
作者：
Guan B;Wu K;Zeng J;Xu S;Mu L;Gao Y;Wang K;Ma Z;Tian J;Shi Q;Guo P;Wang X;He D;Du Y
MicroRNA是一类小的非编码RNA，通过靶向mRNA的翻译抑制或降解来调控基因的表达。许多证据表明，miR-218是许多人类癌症（包括前列腺癌）的肿瘤抑制因子。然而，miR-218在肿瘤血管生成中的潜在作用以及在PCa和其他癌症中的机制仍不清楚。在本研究中，我们证明了miR-218在体外和体内抑制PCa细胞的肿瘤血管生成。mTOR组分2 RICTOR是miR-218的直接靶点，miR-218-RICTOR-VEGFA轴是抑制PCa细胞肿瘤血管生成的机制。RICTOR敲低表型miR-218过表达抑制前列腺癌血管生成总之，我们的研究结果表明，下调miR-218有助于通过RICTOR/VEGFA轴在PCa中的肿瘤血管生成，为PCa肿瘤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PCa的新治疗靶点的潜力。
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.