Up-regulation of p21(WAF1/CIP1) by miRNAs and its implications in bladder cancer cells

FEBS Lett. 2014 Dec 20;588(24):4654-64. doi: 10.1016/j.febslet.2014.10.037. Epub 2014 Nov 11.

Abstract

We have previously reported that synthetic dsRNA can activate p21 expression by targeting the p21 promoter, thereby suppressing the proliferation of human bladder cancer cells. As complementarity between dsRNA and its target sequences is necessary for RNA activation, miRNAs may also trigger p21 expression through the same mechanism. Here, the expression levels of three miRNAs (miR-370, miR-1180 and miR-1236) decreased in bladder cancer tissues compared to healthy controls and the levels of these mRNAs positively correlated with p21 mRNA levels. The three miRNAs induced nuclear p21 expression through p21-promoter binding. Overexpression of the three miRNAs inhibited the proliferation of bladder cancer cells mainly by regulating p21. Therefore, these miRNAs could be candidates for anti-cancer drugs.

Keywords: Bladder cancer; Gene promoter; RNA activation; miRNA; p21.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Base Sequence
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Cellular Senescence / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Promoter Regions, Genetic / genetics
  • Transcriptional Activation
  • Up-Regulation / genetics*
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Cyclin-Dependent Kinase Inhibitor p21
  • MicroRNAs