Inhibition of cell proliferation and migration by miR-509-3p that targets CDK2, Rac1, and PIK3C2A

• Published in: Molecules and cells Vol. 37; no. 4; pp. 314 - 321
• Main Authors: Yoon, Sena, Han, Eunji, Choi, Young-Chul, Kee, Honghwan, Jeong, Yongsu, Yoon, Jaeseung, Baek, Kwanghee
• Format: Journal Article
• Language: English
• Published: United States Korean Society for Molecular and Cellular Biology 01-04-2014; 한국분자세포생물학회
• Subjects: Cell Cycle - genetics; Cell Movement - genetics; Cell Proliferation - genetics; Cyclin-Dependent Kinase 2 - genetics; Cyclin-Dependent Kinase 2 - metabolism; Down-Regulation - genetics; HeLa Cells; Humans; Microarray Analysis; MicroRNAs - genetics; MicroRNAs - metabolism; Neoplasms - genetics; Neoplasms - therapy; Neoplastic Stem Cells; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; rac1 GTP-Binding Protein - genetics; rac1 GTP-Binding Protein - metabolism; RNA, Small Interfering - genetics; Transgenes - genetics; 생물학
• ISSN: 1016-8478; 0219-1032
• DOI: 10.14348/molcells.2014.2360

CDK2 is a key regulator of cell cycle progression. In this study, we screened for miRNAs targeting CDK2 using a luciferase-3'-untranslated region reporter assay. Among 11 hit miRNAs, miR-509-3p reduced CDK2 protein levels and significantly inhibited cancer cell growth. Microarray, Western blotting, and luciferase reporter analyses revealed additional targets of miR-509-3p, including Rac1 and PIK3C2A. Overexpression of miR-509-3p induced G1 cell-cycle arrest and inhibited colony formation and migration. RNAi experiments indicated that the growth-inhibitory effects of miR-509-3p may occur through down-regulation of CDK2, Rac1, and PIK3C2A. Targeting of multiple growth regulatory genes by miR-509-3p may contribute to effective anti-cancer therapy.