MicroRNA-141 promotes the proliferation of non-small cell lung cancer cells by regulating expression of PHLPP1 and PHLPP2

FEBS Lett. 2014 Aug 25;588(17):3055-61. doi: 10.1016/j.febslet.2014.06.020. Epub 2014 Jun 16.

Abstract

The dysregulation of microRNAs (miRNAs) is crucially implicated in the development of various cancers. In this study, we explored the biological role of miR-141 in non-small cell lung cancer (NSCLC). miR-141 expression was significantly up-regulated in NSCLC tissues, and its overexpression accelerated NSCLC cell proliferation in vitro and tumor growth in vivo. We subsequently identified the antagonists of PI3K/AKT signaling, PH domain leucine-rich-repeats protein phosphatase 1 (PHLPP1) and PHLPP2, as direct targets of miR-141. Re-introduction of PHLPP1 and PHLPP2 abrogated miR-141-induced proliferation of NSCLC cells. Together, the results of this study suggest that miR-141 and its targets PHLPP1 and PHLPP2 play critical roles in NSCLC tumorigenesis, and provide potential therapeutic targets for NSCLC treatment.

Keywords: MicroRNA-141; Non-small cell lung cancer; PH domain leucine-rich-repeats protein phosphatase 1; PH domain leucine-rich-repeats protein phosphatase 2; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Male
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Nuclear Proteins / genetics*
  • Phosphoprotein Phosphatases / genetics*
  • Up-Regulation

Substances

  • MIRN141 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • PHLPP1 protein, human
  • PHLPP2 protein, human
  • Phosphoprotein Phosphatases