miR-320a suppresses colorectal cancer progression by targeting Rac1

Carcinogenesis. 2014 Apr;35(4):886-95. doi: 10.1093/carcin/bgt378. Epub 2013 Nov 21.

Abstract

MicroRNAs (miRNAs) have emerged as critical epigenetic regulators involved in cancer progression. miR-320a has been identified to be a novel tumour suppressive miRNA in colorectal cancer (CRC). However, the detailed molecular mechanisms are not fully understood. Here, we reported that miR-320a inversely associated with CRC aggressiveness in both cell lines and clinical specimens. Functional studies demonstrated that miR-320a significantly decreased the capability of cell migration/invasion and induced G0/G1 growth arrest in vitro and in vivo. Furthermore, Rac1 was identified as one of the direct downstream targets of miR-320a and miR-320a specifically binds to the conserved 8-mer at position 1140-1147 of Rac1 3'-untranslated region to regulate Rac1 protein expression. Over-expression of miR-320a in SW620 cells inhibited Rac1 expression, whereas reduction of miR-320a by anti-miR-320a in SW480 cells enhanced Rac1 expression. Re-expression of Rac1 in the SW620/miR-320a cells restored the cell migration/invasion inhibited by miR-320a, whereas knockdown of Rac1 in the SW480/anti-miR-320a cells repressed these cellular functions elevated by anti-miR-320a. Conclusively, our results demonstrate that miR-320a functions as a tumour-suppressive miRNA through targeting Rac1 in CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • DNA Primers
  • Disease Progression
  • Gene Knockdown Techniques
  • Humans
  • MicroRNAs / physiology*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Real-Time Polymerase Chain Reaction
  • rac1 GTP-Binding Protein / genetics*

Substances

  • 3' Untranslated Regions
  • DNA Primers
  • MIRN320 microRNA, human
  • MicroRNAs
  • RAC1 protein, human
  • rac1 GTP-Binding Protein