MiR-130b suppresses prostate cancer metastasis through down-regulation of MMP2

Mol Carcinog. 2015 Nov;54(11):1292-300. doi: 10.1002/mc.22204. Epub 2014 Aug 23.

Abstract

Prostate cancer (PCa) is the most prevalent malignant carcinoma among males in western countries. Currently no treatments can cure advanced prostate cancers, so new diagnostic and therapeutic strategies are in urgent need. At present limited knowledge is available concerning the roles of dysregulated microRNAs in prostate cancer metastasis. In this study, we found that the expression of miR-130b was significantly down-regulated in prostate cancer cell lines and clinical prostate cancer tissues. Enforced over-expression of miR-130b in prostate cancer cells suppressed whereas knock-down of miR-130b increased cell migration and invasion. Using mouse model, we revealed that miR-130b-expressed prostate cancer cells displayed significant reduction in tumor metastasis. Furthermore, we identified and validated matrix metalloproteinase-2 (MMP2) as a direct target of miR-130b. Ectopic expression of MMP2 rescued miR-130b-suppressed cell migration and invasion, and knock-down of MMP2 antagonized the effect of silencing miR-130b.Taken together, our data reveal for the first time that miR-130b exerts a suppressive effect in prostate cancer metastasis through down-regulation of MMP2.

Keywords: MMP2; miR-130b; prostate cancer; tumor metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Down-Regulation / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Prostatic Neoplasms / genetics*

Substances

  • MIRN130 microRNA, human
  • MicroRNAs
  • MMP2 protein, human
  • Matrix Metalloproteinase 2