miR-195 Inhibits Tumor Progression by Targeting RPS6KB1 in Human Prostate Cancer

作者：Chao Cai, Qing-Biao Chen, Zhaodong Han, Yanqiong Zhang, Huichan He, Jia-Hong Chen, Yanru Chen, Sheng-Bang Yang, Yongding Wu, Yanru Zeng, Guoqiang Qin, Yuxiang Liang, Qi-Shan Dai, Funeng Jiang, Shulin Wu, Guohua Zeng, Weide Zhong, Chin‐Lee Wu · 发表于：Clinical Cancer Research · 年份：2015 · DOI：10.1158/1078-0432.ccr-15-0217 · 被引用次数：153 · 研究领域：MicroRNA in disease regulation、Circular RNAs in diseases、Extracellular vesicles in disease

PURPOSE: To investigate the involvement of hsa-miRNA-195-5p (miR-195) in progression and prognosis of human prostate cancer. EXPERIMENTAL DESIGN: qRT-PCR was performed to detect miR-195 expression in both prostate cancer cell lines and clinical tissue samples. Its clinical significance was statistically analyzed. The roles of miR-195 and its candidate target gene, ribosomal protein S6 kinase, 70 kDa, polypeptide 1 (RPS6KB1) in prostate cancer progression were confirmed on the basis of both in vitro and in vivo systems. RESULTS: miR-195 downregulation in prostate cancer tissues was significantly associated with high Gleason score (P = 0.001), positive metastasis failure (P < 0.001), and biochemical recurrence (BCR, P < 0.001). Survival analysis identified miR-195 as an independent prognostic factor for BCR-free survival of prostate cancer patients (P = 0.022). Then, we confirmed the tumor suppressive role of miR-195 through prostate cancer cell invasion, migration, and apoptosis assays in vitro, along with tumor xenograft growth, angiogenesis, and invasion in vivo according to both gain-of-function and loss-of-function experiments. In addition, RPS6KB1 was identified as a novel direct target of miR-195 through proteomic expression profiling combined with bioinformatic target prediction and luciferase reporter assay. Moreover, the reexpression and knockdown of RPS6KB1 could respectively rescue and imitate the effects induced by miR-195. Importantly, RPS6KB1 expression was close...