MiR-32 contributed to cell proliferation of human breast cancer cells by suppressing of PHLPP2 expression

Biomed Pharmacother. 2015 Oct:75:105-10. doi: 10.1016/j.biopha.2015.07.037. Epub 2015 Aug 12.

Abstract

MicroRNAs (miRNAs) have been identified as important regulators that potentially play critical roles in various biological and pathological processes of cancer cells. The aim of the present study was to investigate the expression of miR-32 in breast cancer and its biological role in tumor progression. MiR-32 expression was markedly upregulated in breast cancer tissues and breast cancer cells. Ectopic expression of miR-32 promoted cell proliferation of breast cancer, whereas miR-32-in suppressed this function. Mechanically, data from luciferase reporter assays revealed that miR-32 directly targeted to the 3'-untranslated region (3'-UTR) of PHLPP2. Overexpression of miR-32 led to downregulation of PHLPP2 protein, which resulted in the downregulation of p21 and upregulation of cyclin D1 and p-Rb. In functional assays, PHLPP2-silenced in miR-32-in-transfected ZR-75-30 cells have positive effect to promote cell proliferation, suggesting that direct PHLPP2 downregulation is required for miR-32-induced cell proliferation of breast cancer. Our findings highlighted the importance of miR-32 in promoting tumor progression, and implicate miR-32 as a potential therapeutic target in breast cancer.

Keywords: Breast cancer; Cell proliferation; PHLPP2; miR-32.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Binding Sites
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Cell Proliferation*
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Phosphoprotein Phosphatases / genetics*
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • RNA Interference
  • Retinoblastoma Protein / metabolism
  • Signal Transduction
  • Time Factors
  • Transfection

Substances

  • 3' Untranslated Regions
  • CCND1 protein, human
  • MIRN32 microRNA, human
  • MicroRNAs
  • Retinoblastoma Protein
  • Cyclin D1
  • PHLPP2 protein, human
  • Phosphoprotein Phosphatases