miR-127 regulates cell proliferation and senescence by targeting BCL6

PLoS One. 2013 Nov 25;8(11):e80266. doi: 10.1371/journal.pone.0080266. eCollection 2013.

Abstract

Cellular senescence occurs as a response to extracellular and intracellular stresses and contributes to aging and age-related pathologies. Emerging evidence suggests that cellular senescence also acts as a potent tumor suppression mechanism that prevents the oncogenic transformation of primary human cells. Recent reports have indicated that miRNAsact as key modulators of cellular senescence by targeting critical regulators of the senescence pathways. We previously reported that miR-127 is up-regulated in senescent fibroblasts. In this report, we identified miR-127 as a novel regulator of cellular senescence that directly targets BCL6. We further showed that miR-127 is down-regulated in breast cancer tissues and that this down-regulation is associated with up-regulation of BCL6. Over-expression of miR-127 or depletion of BCL6 inhibits breast cancer cell proliferation. Our data suggest that miR-127 may function as a tumor suppressor that modulates the oncogene BCL6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Cellular Senescence / genetics*
  • DNA-Binding Proteins / metabolism*
  • Female
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • MicroRNAs / physiology*
  • Proto-Oncogene Proteins c-bcl-6

Substances

  • BCL6 protein, human
  • DNA-Binding Proteins
  • MIRN127 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-6

Grant support

This work was supported in part by grants from the National Basic Research Program of China [2012CB911203, 2010CB912802] and the National Natural Science Foundation of China [31201038, 31071200, 31171320]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.