基因miR-205表达下调抑制前列腺肿瘤生长

本文旨在研究抑癌基凶has-miR-205在前列腺癌中的分子和功能机制。通过对早期和晚期前列腺癌组织进行miRNAs表达的基因芯片分析，从中选出异常表达的miR-205进行实时定量PCR分析，并对其在前列腺癌中的功能和靶基因c-SRC及其下游FAK／ERKI／2通路进行分析。结果发现miR-205在晚期前列腺癌中呈现低表达，其表达量与临床病理分期和总PSA及游离PSA呈负关联。体外功能试验分析显示高表达miR-205或是敲除C-SRC基因的表达可以抑制前列腺癌细胞的增殖与转移。裸鼠体内实验分析高表达miR-205可以抑制前列腺癌肿瘤形成。通过荧光素酶报告基因和Western blotting分析证实C—SRC是miR-205的靶基因，高表达的miR-205抑Nc-SRC及下游通路FAK，P—FAK，ERK1／2和P—ERK1／2的蛋白表达。抑癌基因miR-205在前列腺癌中低表达，并且通过靶基因C-SRC来抑制前列腺痛细胞的增殖和转移。

miR-205 is frequently downregulated in prostate cancer and acts as a tumor suppressor by inhibiting tumor growth

The purpose of this study was to elucidate the molecular mechanisms of microRNA-205 （miR-205） as a tumor suppressor in prostate cancer （PCa）o In the present study, microRNA microarray analysis suggested that the expression of miR-205 was significantly decreased in advanced PCa compared with early PCa. Real-time PCR analysis also indicated that miR-205 expression was significantly decreased in PCa tissues compared with non-cancerous tissues. Moreover, the expression of miR-205 has been demonstrated to be associated with the clinicopathological stage and total/free prostate-specific antigen （PSA） level of PCa. Functional analyses showed that both the overexpression of miR-205 and the knockdown of c-SRC in PCa cell lines could inhibit cell growth, colony formation, migration, invasion and the cell cycle as well as induce cell apoptosis in vitro. Furthermore, over-expressing miR-205 reduced tumorigenicity in vivo. Through a luciferase activity assay and Western blotting, c-SRCwas identified as a target of miR-205 in cells. The overexpression of miR-205 suppressed c-SRC and its downstream signaling molecules, including FAK, p-FAK, ERK1/2 and D-ERK1/2, and attenuated cell proliferation, invasion and tumor growth.