miR‑494 is an independent prognostic factor and promotes cell migration and invasion in colorectal cancer by directly targeting PTEN

Int J Oncol. 2014 Dec;45(6):2486-94. doi: 10.3892/ijo.2014.2665. Epub 2014 Sep 22.

Abstract

Accumulating evidence has shown that micro-RNAs (miRNAs) are involved in multiple processes in cancer development and progression. Upregulation of miRNA-494 (miR-494) has been identified as an oncogenic miRNA and is associated with poor prognosis in several types of human cancer. However, the specific function of miR-494 in colorectal cancer remains unclear. In this study we found that the expression of miR-494 in colorectal cancer tissues and cell lines was much higher than in normal control tissues and cells, respectively. In addition, upregulation of miR-494 more frequently occurred in tissue specimens with adverse clinical stage and the presence of distant metastasis. Moreover, multivariate survival analyses demonstrated that overexpression of miR-494 is an independent prognostic factor for both progression-free and overall survival. In addition miR-494 promoted invasion and migration in colorectal cancer cells, and miR-494 directly inhibited the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression by targeting its 3'-untranslated region (3'-UTR). Moreover, PTEN is down regulated and inversely correlated with miR-494 expression in tissues. Thus, for the first time, we provided convincing evidence that upregulation of miR-494 was associated with tumor aggressiveness and tumor metastasis and promoted cell migration and invasion by targeting PTEN gene in colorectal cancer, and miR-494 is an independent prognostic marker for colorectal cancer patients.

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Aged
  • Cell Movement / genetics*
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Middle Aged
  • Neoplasm Invasiveness / genetics*
  • PTEN Phosphohydrolase / biosynthesis*
  • PTEN Phosphohydrolase / genetics
  • RNA Interference

Substances

  • 3' Untranslated Regions
  • MIRN494 microRNA, human
  • MicroRNAs
  • PTEN Phosphohydrolase
  • PTEN protein, human