MicroRNA-449a acts as a tumor suppressor in human bladder cancer through the regulation of pocket proteins

Cancer Lett. 2012 Jul 1;320(1):40-7. doi: 10.1016/j.canlet.2012.01.027. Epub 2012 Jan 20.

Abstract

Frequent downregulation of microRNA-449a (miR-449a) was detected in 14 human bladder cancer tissues. The restoration of miR-449a inhibited cell growth and induced G1-phase arrest in T24 and 5637 human bladder cancer cells. CDK6 and CDC25a were downregulated after miR-449a treatment, resulting in the functional accumulation of the pocket proteins Rb and p130. The growth of T24 tumor xenografts was suppressed by exogenous miR-449a, and the nuclear proliferation antigen Ki-67 was downregulated in miR-449a-treated tumors. These results suggest a tumor-suppressive role for miR-449a in human bladder cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Base Sequence
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Crk-Associated Substrate Protein / genetics*
  • Crk-Associated Substrate Protein / metabolism
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors
  • Down-Regulation
  • Female
  • G1 Phase Cell Cycle Checkpoints / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / administration & dosage
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Middle Aged
  • Mitochondrial Proteins
  • Molecular Sequence Data
  • Phosphorylation
  • Retinoblastoma Protein / genetics*
  • Retinoblastoma Protein / metabolism
  • Transplantation, Heterologous
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology
  • cdc25 Phosphatases / antagonists & inhibitors

Substances

  • BCAR1 protein, human
  • Crk-Associated Substrate Protein
  • MIRN449 microRNA, human
  • MicroRNAs
  • Mitochondrial Proteins
  • Retinoblastoma Protein
  • SPATA18 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6
  • CDC25A protein, human
  • cdc25 Phosphatases