Elevated oncofoetal miR-17-5p expression regulates colorectal cancer progression by repressing its target gene P130

Nat Commun. 2012:3:1291. doi: 10.1038/ncomms2276.

Abstract

MicroRNAs (miRNAs) are essential for regulating normal embryonic development and carcinogenesis. Here we report that miR-17-5p, an oncofoetal miRNA, is a key regulator of colorectal cancer progression. We show that miR-17-5p is an oncogenic miRNA that regulates tumorigenesis and progression by targeting the gene encoding P130 and subsequently activating the Wnt/β-catenin pathway. Using specimens from two large cohorts of colorectal cancer patients, we found that patients whose tumours had high miR-17-5p expression had shorter overall survival rates but showed a better response to adjuvant chemotherapy than did patients whose tumours had low miRNA expression. We also observed a strong inverse correlation between miR-17-5p and P130 expression. The current findings suggest that miR-17-5p is a crucial determinant of colorectal cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cell Line, Tumor
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / physiopathology
  • Crk-Associated Substrate Protein / antagonists & inhibitors*
  • Crk-Associated Substrate Protein / biosynthesis
  • Down-Regulation / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / biosynthesis
  • MicroRNAs / physiology*
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / physiopathology
  • Prognosis
  • Real-Time Polymerase Chain Reaction
  • Survival Analysis
  • Wnt Signaling Pathway / physiology

Substances

  • Crk-Associated Substrate Protein
  • MIRN17 microRNA, human
  • MicroRNAs