miR-491-5p functions as a tumor suppressor by targeting JMJD2B in ERα-positive breast cancer

FEBS Lett. 2015 Mar 24;589(7):812-21. doi: 10.1016/j.febslet.2015.02.014. Epub 2015 Feb 25.

Abstract

The involvement of miR-491-5p in breast cancer development is unclear. This study showed that miR-491-5p is significantly downregulated in ERα-positive breast cancer tissues and cell lines and is generally hypermethylated in ERα-positive breast cancer. MiR-491-5p overexpression significantly suppressed estrogen signaling and estrogen-stimulated proliferation of breast cancer cells. Furthermore, the histone demethylase JMJD2B was identified as a direct target of miR-491-5p. The ectopic expression of JMJD2B abrogated the phenotypic changes induced by miR-491-5p in breast cancer cells. Collectively, our data indicate that miR-491-5p plays a tumor suppressor role in the development and progression of breast caner and may be a novel therapeutic target against ERα-positive breast cancer.

Keywords: Breast cancer; Estrogen receptor α; Estrogen signaling; JMJD2B; miR-491-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Aged
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Methylation
  • Decitabine
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / genetics*
  • Jumonji Domain-Containing Histone Demethylases / metabolism
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Middle Aged

Substances

  • 3' Untranslated Regions
  • Estrogen Receptor alpha
  • MIRN491 microRNA, human
  • MicroRNAs
  • Decitabine
  • Jumonji Domain-Containing Histone Demethylases
  • KDM4B protein, human
  • Azacitidine