Up-regulated miR-17 promotes cell proliferation, tumour growth and cell cycle progression by targeting the RND3 tumour suppressor gene in colorectal carcinoma

Biochem J. 2012 Mar 1;442(2):311-21. doi: 10.1042/BJ20111517.

Abstract

Emerging evidence indicates that the miR-17 family may have a causal role in human cancer tumorigenesis, but their specific effects on the occurrence of CRC (colorectal carcinoma) are still poorly understood. In the present study, we profiled CRC tissue samples by miRNA (microRNA) microarray and found that four members of the miR-17 family had higher expression in CRC tissues than in normal tissues. This finding was further validated by qRT-PCR (quantitative reverse transcription PCR). Transfecting CRC cells with an inhibitor of miR-17 lowered their ability to proliferate and induced G0/G1 arrest. We also confirmed that miR-17 exerted this function by directly targeting RND3 in vitro, and that the expression of miR-17 was negatively correlated with that of RND3 in CRC tissues and CRC cells. Moreover, miR-17 inhibition led to tumour growth suppression and up-regulation of RND3 expression in a nude mouse xenograft model. RND3 expression was found to be significantly lower in CRC tissues than in normal tissues and adenomas, indicating that RND3 may act as a tumour suppressor gene in CRC. In conclusion, the present study suggests that miR-17 plays an important role in CRC carcinogenesis by targeting RND3 and may be a therapeutic agent for CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Cycle Checkpoints / genetics
  • Cell Cycle Checkpoints / physiology
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Female
  • Genes, Tumor Suppressor*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Neoplasm Transplantation
  • RNA, Neoplasm / genetics*
  • RNA, Neoplasm / metabolism*
  • RNA, Small Interfering / genetics
  • Transplantation, Heterologous
  • Up-Regulation
  • rho GTP-Binding Proteins / antagonists & inhibitors
  • rho GTP-Binding Proteins / genetics*

Substances

  • MIRN17 microRNA, human
  • MicroRNAs
  • RNA, Neoplasm
  • RNA, Small Interfering
  • RND3 protein, human
  • rho GTP-Binding Proteins