Wang Ning, Li Qi, Feng Ning-Han, Cheng Gong, Guan Zhao-Long, Wang Yang, Qin Chao, Yin Chang-Jun, Hua Li-Xin
Asian J Androl. 2013 Nov;15(6):735-41. doi: 10.1038/aja.2013.80. Epub 2013 Aug 26.
The purpose of this study was to elucidate the molecular mechanisms of microRNA-205 (miR-205) as a tumor suppressor in prostate cancer (PCa). 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-SRC was 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 p-ERK1/2, and attenuated cell proliferation, invasion and tumor growth.
本研究的目的是阐明微小RNA-205（miR-205）作为前列腺癌（PCa）肿瘤抑制因子的分子机制。在本研究中，微小RNA微阵列分析表明，与早期PCa相比，晚期PCa中miR-205的表达显著降低。实时PCR分析也表明，与非癌组织相比，PCa组织中miR-205的表达显著降低。此外，已证明miR-205的表达与PCa的临床病理分期以及总/游离前列腺特异性抗原（PSA）水平相关。功能分析表明，PCa细胞系中miR-205的过表达和c-SRC的敲低均可抑制细胞生长、集落形成、迁移、侵袭以及细胞周期，并在体外诱导细胞凋亡。此外，过表达miR-205可降低体内致瘤性。通过荧光素酶活性测定和蛋白质印迹法，确定c-SRC为细胞中miR-205的靶标。miR-205的过表达抑制了c-SRC及其下游信号分子，包括FAK、p-FAK、ERK1/2和p-ERK1/2，并减弱了细胞增殖、侵袭和肿瘤生长。
