Guo Jia, Wang Min, Liu Xiuheng
Department of Urology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan, 430060, Hubei, People's Republic of China.
J Exp Clin Cancer Res. 2015 Sep 4;34(1):91. doi: 10.1186/s13046-015-0209-7.
Elucidation of the downstream targets regulated by the metastasis-suppressive miRNAs can shed light on the metastatic processes in prostate cancer (PCa). We conducted microarray analyses and found that miR-195 was significantly decreased in metastatic PCa. Low miR-195 expression is an independent prognostic factor for poor biochemical recurrence-free and overall survival. Forced expression of miR-195 in PCa cells drastically inhibits proliferation, migration and invasion in vitro and inhibits tumor growth and metastasis in vivo. BCOX1 is identified as a direct target of miR-195 in PCa, and is found to be drastically increased in metastatic PCa. BCOX1 knockdown phenotypically copies miR-195-induced phenotypes, whereas forced expression of BCOX1 reverses the effects of miR-195. Collectively, this is the first report unveils that loss of miR-195 expression and thus uncontrolled BCOX1 upregulation might drive PCa metastasis.
对由转移抑制性微小RNA调控的下游靶点的阐释，有助于揭示前列腺癌（PCa）的转移过程。我们进行了微阵列分析，发现miR-195在转移性PCa中显著降低。低miR-195表达是生化无复发生存和总生存不良的独立预后因素。在PCa细胞中强制表达miR-195可显著抑制体外增殖、迁移和侵袭，并抑制体内肿瘤生长和转移。BCOX1被确定为PCa中miR-195的直接靶点，且发现在转移性PCa中显著增加。敲低BCOX1在表型上复制了miR-195诱导的表型，而强制表达BCOX1则逆转了miR-195的作用。总体而言，这是首份报告揭示miR-195表达缺失以及由此导致的BCOX1不受控制地上调可能驱动PCa转移。
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