MicroRNA-149 suppresses colorectal cancer cell migration and invasion by directly targeting forkhead box transcription factor FOXM1

Cell Physiol Biochem. 2015;35(2):499-515. doi: 10.1159/000369715. Epub 2015 Jan 16.

Abstract

Background/aims: The aim of this study is to investigate the clinicopathological and prognostic values of miR-149 expression and its roles in colorectal cancer (CRC) progression.

Methods: qRT-PCR was performed to detect miR-149 expression in CRC cell lines or tissues. Also, the clinical significance of miR-149 expression was investigated. The study further explored whether miR-149 inhibits migration and invasion of CRC cells by targeting the mammalian Forkhead Box M1 (FOXM1).

Results: miR-149 was significantly downregulated in CRC tissues, and low miR-149 expression was observed to be significantly correlated with lymph node or distant metastasis and advanced TNM stage of CRC patients. Patients with low miR-149 expression showed poorer prognosis than those with high miR-149 expression, and multivariate analyses indicated that status of miR-149 expression might be an independent prognostic factor. Gain- and loss - of - function assays indicated that miR-149 significantly inhibited growth, migration and invasion of CRC cells by targeting FOXM1. Furthermore, FOXM1 was significantly uiregulated in CRC tissues and inversely correlated with miR-149 expression.

Conclusions: mR-149 was an independent prognostic factor and could inhibit migration and invasion of CRC cells, at least partially by targeting FOXM1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Line, Tumor
  • Cell Movement
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Female
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors / genetics*
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Survival Analysis

Substances

  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • MIRN149 microRNA, human
  • MicroRNAs