MicroRNA-372 is down-regulated and targets cyclin-dependent kinase 2 (CDK2) and cyclin A1 in human cervical cancer, which may contribute to tumorigenesis

J Biol Chem. 2011 Jul 22;286(29):25556-63. doi: 10.1074/jbc.M111.221564. Epub 2011 Jun 6.

Abstract

MicroRNAs are a class of noncoding RNAs that are ~22 nucleotides in length. MicroRNAs have been shown to play important roles in cell differentiation and in cancer. Recently, studies have shown that miR-372 is tumorigenic in human reproductive system cancers. However, we provide evidence that miR-372 acts as a tumor suppressor gene in cervical carcinoma. miR-372 was found down-regulated in cervical carcinoma tissues as compared with adjacent normal cervical tissues. Growth curve and FACS assays indicated that ectopic expression of miR-372 suppressed cell growth and induced arrest in the S/G₂ phases of cell cycle in HeLa cells. We used bioinformatic predictions to determine that CDK2 and cyclin A1 were possible targets of miR-372 and confirmed this prediction using a fluorescent reporter assay. Taken together, these findings indicate that an anti-oncogenic role of miR-372 may be through control of cell growth and cell cycle progression by down-regulating the cell cycle genes CDK2 and cyclin A1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / genetics
  • Cell Proliferation
  • Cyclin A1 / genetics
  • Cyclin A1 / metabolism*
  • Cyclin-Dependent Kinase 2 / deficiency
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 2 / metabolism*
  • Down-Regulation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • MicroRNAs / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*

Substances

  • Cyclin A1
  • MIRN372 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Cyclin-Dependent Kinase 2