MicroRNA-490-3P targets CDK1 and inhibits ovarian epithelial carcinoma tumorigenesis and progression

Cancer Lett. 2015 Jun 28;362(1):122-30. doi: 10.1016/j.canlet.2015.03.029. Epub 2015 Mar 25.

Abstract

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.

Keywords: CDK1; Cell proliferation; MiR-490-3P; Ovarian epithelial carcinoma; Tumorigenesis and progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Base Sequence
  • CDC2 Protein Kinase
  • Carcinogenesis
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Cyclin-Dependent Kinases / biosynthesis
  • Cyclin-Dependent Kinases / genetics*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Genotype
  • Heterografts
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Sequence Data
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / metabolism
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Transfection

Substances

  • 3' Untranslated Regions
  • MIRN490 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • Cyclin-Dependent Kinases