MicroRNA-185 suppresses proliferation, invasion, migration, and tumorigenicity of human prostate cancer cells through targeting androgen receptor
MicroRNA-185 suppresses proliferation, invasion, migration, and tumorigenicity of human prostate cancer cells through targeting androgen receptor
复制标题
MicroRNA-185通过靶向雄激素受体抑制人前列腺癌细胞的增殖、侵袭、迁移和致瘤性
DOI：
10.1007/s11010-013-1576-z
复制
发表时间：
2013-05-01
影响因子：
4.3
通讯作者：
Wang, Quanxing
中科院分区：
文献类型：
--
作者：
Qu, Fajun;Cui, Xingang;Wang, Quanxing
以往的研究表明，雄激素受体（AR）通过多种机制参与前列腺癌（CaP）的进展。然而，AR是如何被调节的还没有被完全理解。在这项研究中，发现miR-185在临床CaP样本中下调。靶点预测显示AR具有与miR-185推定的互补序列，这通过以下双荧光素酶报告基因测定得到证实。过表达miR-185可降低LNCaP细胞AR蛋白表达，但对mRNA表达无影响。过表达miR-185可抑制LNCaP细胞的增殖。细胞周期分析显示细胞周期阻滞于G 0/G1期。miR-185还可以抑制细胞的侵袭和迁移能力。此外，miR-185抑制CaP异种移植模型中的致瘤性。CDC 6是AR的靶点之一，也是细胞周期的重要调控分子，miR-185过表达可下调CDC 6的表达。我们的研究结果表明，miR-185可以作为一个肿瘤抑制基因在CaP中直接靶向AR，并作为一个潜在的治疗靶点CaP。
Previous studies have shown that androgen receptor (AR) is involved in the progression of prostate cancer (CaP) by several mechanisms. However, how AR is regulated has not been fully understood. In this study, miR-185 was found to be down-regulated in clinical CaP samples. Targets prediction revealed that AR had putative complementary sequences to miR-185, which was confirmed by the following dual luciferase reporter assay. Overexpression of miR-185 could reduce the expression of AR protein but not mRNA in LNCaP cells. The proliferation of LNCaP cells was inhibited by overexpression of miR-185. Cell cycle analysis revealed cell cycle arrest at G0/G1 phase. The invasive and migration abilities of cells could also be suppressed by miR-185. Furthermore, miR-185 inhibited tumorigenicity in a CaP xenografts model. CDC6, one target of AR and an important regulatory molecule for cell cycle, was found to be down-regulated by overexpression of miR-185. Our findings suggest that miR-185 could function as a tumor-suppressor gene in CaP by directly targeting AR, and act as a potential therapeutic target for CaP.