MiR-145 inhibits human colorectal cancer cell migration and invasion via PAK4-dependent pathway

Cancer Med. 2017 Jun;6(6):1331-1340. doi: 10.1002/cam4.1029. Epub 2017 Apr 24.

Abstract

MicroRNA-145 (miR-145), as a tumor-suppressive miRNA, has been demonstrated down-regulated in colorectal cancer (CRC) cells, and could inhibit CRC cells growth. However, the molecular pathway in which miR-145 modulates CRC malignant transformation has not been fully revealed. Here, we reported an intense correlation between the expressions of PAK4 and miR-145 in human CRC cell lines. Transwell assay verified overexpression of miR-145, as well as knockdown of PAK4, significantly suppressed cell migration and invasion ability. The impaired migration and invasion ability of SW1116 cells was affected through the down-regulation of phosphorylation level of LIMK1 and cofilin in a PAK4-dependent manner. Collectively, we have demonstrated that miR-145 suppressed CRC migration and invasion through PAK4 pathway, which provides an attractive microRNA-based therapeutic target for CRC.

Keywords: colorectal cancer; cytoskeleton; miR-145; migration.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cofilin 1 / metabolism*
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Humans
  • Lim Kinases / metabolism*
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Signal Transduction
  • p21-Activated Kinases / genetics
  • p21-Activated Kinases / metabolism*

Substances

  • Cofilin 1
  • MIRN145 microRNA, human
  • MicroRNAs
  • PAK4 protein, human
  • LIMK1 protein, human
  • Lim Kinases
  • p21-Activated Kinases