Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway

Oncotarget. 2015 Feb 28;6(6):3904-17. doi: 10.18632/oncotarget.2880.

Abstract

Here we found that levels of miR-23a were decreased in prostate cancer cell lines and tumor tissues. These low levels were associated with poor patients' prognosis. MiR-23a inhibited migration and invasion of prostate cancer in vivo and in orthotopic prostate cancer mice model. MiR-23a decreased levels of p21-activated kinase 6 (PAK6). Expression of miR-23a inhibited phosphorylation of LIM kinase 1 (LIMK1) and cofilin, in turn suppressing formation of stress fibers and actin filaments, which was required for cell motility and invasion. PAK6 bound to LIMK1 and activated it via phosphorylation at Thr-508. Also, PAK6 and LIMK1 were colocalized in the cytoplasma. Thus, miR-23a regulated cytoskeleton by affecting LIMK1 and cofilin. In summary, we have identified the miR-23a-PAK6-LIMK1 pathway of prostate cancer metastasis. Potential therapeutic approach by targeting miR-23 is suggested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Cell Line, Tumor
  • Down-Regulation
  • Gene Expression Profiling
  • HEK293 Cells
  • Heterografts
  • Humans
  • Lim Kinases / genetics
  • Lim Kinases / metabolism*
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Metastasis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Signal Transduction
  • p21-Activated Kinases / genetics
  • p21-Activated Kinases / metabolism*

Substances

  • MicroRNAs
  • Mirn23b microRNA, mouse
  • LIMK1 protein, human
  • Lim Kinases
  • PAK6 protein, human
  • p21-Activated Kinases