MicroRNA‑328 directly targets p21‑activated protein kinase 6 inhibiting prostate cancer proliferation and enhancing docetaxel sensitivity

Mol Med Rep. 2015 Nov;12(5):7389-95. doi: 10.3892/mmr.2015.4390. Epub 2015 Sep 30.

Abstract

Prostate cancer (Pca) has one of the highest mortality rates for malignant cancers worldwide. Previous research has demonstrated that numerous genes are aberrantly expressed during Pca onset and development. p21‑activated protein kinase 6 (PAK6) is known to be overexpressed in primary and metastatic Pca, however the mechanism of this aberrant expression remains unknown. In the present study, immunohistochemistry demonstrated that PAK6 is overexpressed in castration‑resistant Pca (CRPC). Furthermore, PAK6 overexpression was regulated by microRNA (miR)‑328. Luciferase reporter assay and western blot analysis indicated that PAK6 was directly targeted by miR‑328. Forced expression of miR‑328 enhanced docetaxel sensitivity, inhibited cell proliferation and promoted cell apoptosis without affecting the cell cycle. This indicates that miR‑328 performs important functions in CRPC progression via PAK6 regulation. This mechanism may be used to enhance the effect of docetaxel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation
  • Docetaxel
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics*
  • Taxoids / pharmacology
  • p21-Activated Kinases / genetics*

Substances

  • Antineoplastic Agents
  • MIRN328 microRNA, human
  • MicroRNAs
  • Taxoids
  • Docetaxel
  • PAK6 protein, human
  • p21-Activated Kinases