miR-21 downregulates the tumor suppressor P12 CDK2AP1 and stimulates cell proliferation and invasion

J Cell Biochem. 2011 Mar;112(3):872-80. doi: 10.1002/jcb.22995.


The present study was undertaken to investigate the regulation of P12(CDK2AP1) by miRNAs. A conserved target site for miR-21 within the CDK2AP1-3'-UTR at nt 349-370 was predicted by bioinformatics software and an inverse correlation of miR-21 and CDK2AP1 protein was observed. Highly specific amplification and quantification of miR-21 was achieved using real-time RT-PCR. Transfection of HaCaT cells with pre-miR-21 significantly suppressed a luciferase reporter including the CDK2AP1-3'-UTR, whereas transfection of Tca8113 with anti-miR-21 increased activity of this reporter. This was abolished when a construct mutated at the miR-21/nt 349-370 target site was used instead. Anti-miR-21-transfected Tca8113 cells showed an increase of CDK2AP1 protein and reduced proliferation and invasion. Resected primary tumors and tumor-free surgical margins of 18 patients with head and neck squamous cell carcinomas demonstrated an inverse correlation between miR-21 and P12(CDK2AP1). This study shows that P12(CDK2AP1) is downregulated by miR-21 and that miR-21 promotes proliferation and invasion in cultured cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Aged
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Down-Regulation
  • Female
  • Genes, Reporter
  • Humans
  • Luciferases / genetics
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness / pathology*
  • RNA Interference
  • Tumor Suppressor Proteins / genetics*


  • 3' Untranslated Regions
  • CDK2AP1 protein, human
  • MIRN21 microRNA, human
  • MicroRNAs
  • Tumor Suppressor Proteins
  • Luciferases