Down-regulation of miR-29c in human bladder cancer and the inhibition of proliferation in T24 cell via PI3K-AKT pathway

Med Oncol. 2014 Jul;31(7):65. doi: 10.1007/s12032-014-0065-x. Epub 2014 Jun 22.

Abstract

The purpose of this study was to explore new tumor suppressor microRNA in bladder cancer and to conduct functional analysis of its suppressive role. To investigate the expression of miR-29c, qRT-PCR was used in 30 pairs of bladder cancer tissues and normal tissues (adjacent bladder tissue samples). The expression of miR-29c was down regulated in bladder cancer tissues compared with normal tissues. Also, the low-level expression of miR-29c was associated with tumor stage (P = 0.002), and ectopic over-expression of miR-29c in T24 cells can significantly inhibit cell proliferation, decrease motility, suppress the G1/S cell cycle transition and induce apoptosis. Furthermore, it could cause a decrease in AKT and GSK-3β phosphorylation. While LY294002 reduced the protein level of pAKT, the over-expression of miR-29c can further decrease its level in T24 cells pretreated with LY294002. Our study also indicated that the proliferation inhibition of T24 may take place via AKT-GSK3β pathway. Thus, miR-29c could be an active player in disease state of bladder cancer and it may be a promising tumor suppressor in bladder cancer.

MeSH terms

  • Aged
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Chromones / pharmacology
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Morpholines / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Reference Values
  • Signal Transduction / genetics
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology*
  • Urinary Bladder Neoplasms / surgery

Substances

  • Chromones
  • MIRN29a microRNA, human
  • MicroRNAs
  • Morpholines
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3