Estrogen receptor-regulated microRNAs contribute to the BCL2/BAX imbalance in endometrial adenocarcinoma and precancerous lesions

Cancer Lett. 2012 Jan 28;314(2):155-65. doi: 10.1016/j.canlet.2011.09.027. Epub 2011 Sep 29.

Abstract

Uncontrolled estrogen exposure can induce an imbalance in BCL2/BAX expression in endometrial cells, leading to precancerous lesions and type I endometrial adenocarcinoma. This study aimed to explore the mechanism underlying this phenomenon. We show that the activated estrogen receptor can suppress the expression of BAX by upregulating a group of microRNAs including hsa-let-7 family members and hsa-miR-27a, thereby promoting an increased BCL2/BAX ratio as well as enhanced survival and proliferation in the affected cells. These ER-regulated hsa-let-7 microRNAs can be detected in most hyperplastic endometria, suggesting their potential utility as indicators of estrogen over-exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Adult
  • Cell Line, Tumor
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / pathology*
  • Female
  • Genes, bcl-2*
  • Humans
  • MicroRNAs / physiology*
  • Middle Aged
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology*
  • Promoter Regions, Genetic
  • Receptors, Estrogen / physiology*
  • bcl-2-Associated X Protein / genetics*

Substances

  • BAX protein, human
  • MicroRNAs
  • Receptors, Estrogen
  • bcl-2-Associated X Protein
  • mirnlet7 microRNA, human