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

Nengquan Sheng1, Gewen Tan1, Weiqiang You1

  • 1Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

Cancer Medicine
|April 26, 2017
PubMed

Insights

MicroRNA-145 (miR-145) suppresses colorectal cancer (CRC) growth by inhibiting cell migration and invasion. This study reveals miR-145 targets the PAK4 pathway, offering a potential therapeutic strategy for CRC.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • MicroRNA-145 (miR-145) is a tumor-suppressive microRNA.
  • miR-145 is downregulated in colorectal cancer (CRC) cells, inhibiting their growth.
  • The precise molecular mechanisms by which miR-145 influences CRC progression remain incompletely understood.

Purpose of the Study:

  • To investigate the molecular pathway through which miR-145 modulates colorectal cancer (CRC) malignant transformation.
  • To explore the correlation between miR-145 and PAK4 expression in CRC.
  • To elucidate the role of the PAK4 pathway in miR-145-mediated suppression of CRC cell migration and invasion.

Main Methods:

  • Correlation analysis of miR-145 and PAK4 expression in human CRC cell lines.
  • Transwell assays to assess cell migration and invasion upon miR-145 overexpression or PAK4 knockdown.
  • Western blot analysis to evaluate the phosphorylation levels of LIMK1 and cofilin.

Main Results:

  • A strong inverse correlation was observed between miR-145 and PAK4 expression in CRC cells.
  • Overexpression of miR-145 and knockdown of PAK4 significantly reduced CRC cell migration and invasion.
  • The observed suppression of migration and invasion was mediated by the downregulation of LIMK1 and cofilin phosphorylation in a PAK4-dependent manner.

Conclusions:

  • miR-145 suppresses colorectal cancer (CRC) cell migration and invasion by targeting the PAK4 signaling pathway.
  • The miR-145/PAK4 axis represents a novel molecular mechanism in CRC progression.
  • This pathway holds promise as a potential microRNA-based therapeutic target for CRC treatment.
Keywords:
colorectal cancercytoskeletonmiR-145migration

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