MicroRNA-34a targets FMNL2 and E2F5 and suppresses the progression of colorectal cancer

Exp Mol Pathol. 2015 Aug;99(1):173-9. doi: 10.1016/j.yexmp.2015.06.014. Epub 2015 Jun 20.

Abstract

Colorectal cancer (CRC) is one of the most common malignancies. Increasing evidences indicate that dysregulation of miRNAs is a frequent event in CRC and contributes to the pathogenesis of CRC. In this study, we found that over-expression of miR-34a inhibited cell proliferation and invasion, induced a cell cycle arrest and triggered apoptosis, while knockdown of miR-34a showed the opposite effects. Moreover, ectopic miR-34a suppressed tumor growth and metastasis of CRC cells in vivo. FMNL2 and E2F5 were identified as direct targets of miR-34a. Reintroduction of FMNL2 or E2F5 without 3'UTR region reversed the inhibitory effects of miR-34a on cell proliferation and invasion. MiR-34a was down-regulated in CRC cells and inversely correlated with FMNL2 and E2F5 expressions. Our study suggests that miR-34a is an important tumor suppressor of CRC progression by targeting FMNL2 and E2F5, thus providing new insight into the molecular mechanisms underlying CRC progression and establishing a strong potential for the application of miR-34a as a novel therapeutic marker against CRC.

Keywords: Colorectal cancer; E2F5; FMNL2; MiR-34a; Progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis / genetics
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Down-Regulation
  • E2F5 Transcription Factor / genetics
  • E2F5 Transcription Factor / metabolism*
  • Formins
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Proteins / genetics
  • Proteins / metabolism*

Substances

  • 3' Untranslated Regions
  • E2F5 Transcription Factor
  • E2F5 protein, human
  • FMNL2 protein, human
  • Formins
  • MIRN34 microRNA, human
  • MicroRNAs
  • Proteins