Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Cancer Lett. 2015 Jun 28;362(1):122-30. doi: 10.1016/j.canlet.2015.03.029. Epub 2015 Mar 25.
The expression of microRNA-490-3P has been reported to regulate hepatocellular carcinoma cell proliferation, migration and invasion, and its overexpression significantly inhibits A549 lung cancer cell proliferation. Here, we demonstrated for the first time that miR-490 mRNA expression was significantly lower in ovarian carcinoma and borderline tumors compared to benign tumors, and lower in metastatic ovarian carcinoma (omentum) than primary ovarian carcinoma, and was negatively associated with differentiation and International Federation of Gynecology and Obstetrics (FIGO) staging. MiR-490-3P overexpression promoted G1/S or G2/M arrest and apoptosis; reduced cell proliferation, migration and invasion; reduced CDK1, Bcl-xL, MMP2/9, CCND1, SMARCD1 mRNA or protein expression; and induced P53 expression. Dual-luciferase reporter assay indicated miR-490-3P directly targeted CDK1. In vivo studies showed that miR-490-3P transfection suppressed tumor development and CDK1, Bcl-xL, MMP2/9 expression while inducing P53 expression. These findings indicate that miR-490-3P may target CDK1 and inhibit ovarian epithelial carcinoma tumorigenesis and progression.
miR-490-3P 的表达已被报道可调节肝癌细胞的增殖、迁移和侵袭,其过表达可显著抑制 A549 肺癌细胞的增殖。在这里,我们首次证明 miR-490 mRNA 的表达在卵巢癌和交界性肿瘤中明显低于良性肿瘤,在转移性卵巢癌(大网膜)中低于原发性卵巢癌,并且与分化和国际妇产科联合会(FIGO)分期呈负相关。miR-490-3P 的过表达促进了 G1/S 或 G2/M 期阻滞和细胞凋亡;降低了细胞增殖、迁移和侵袭;降低了 CDK1、Bcl-xL、MMP2/9、CCND1、SMARCD1 mRNA 或蛋白的表达;并诱导了 P53 的表达。双荧光素酶报告基因实验表明 miR-490-3P 可直接靶向 CDK1。体内研究表明,miR-490-3P 转染可抑制肿瘤的发展和 CDK1、Bcl-xL、MMP2/9 的表达,同时诱导 P53 的表达。这些发现表明,miR-490-3P 可能靶向 CDK1,抑制卵巢上皮性癌的发生和发展。