Elevated expression of long intergenic non-coding RNA HOTAIR in a basal-like variant of MCF-7 breast cancer cells

Mol Carcinog. 2015 Dec;54(12):1656-67. doi: 10.1002/mc.22237. Epub 2014 Oct 18.


Epigenetic regulation of gene expression is critical to phenotypic maintenance and transition of human breast cancer cells. HOX antisense intergenic RNA (HOTAIR) is a long intergenic non-coding RNA that epigenetically represses gene expression via recruitment of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase. Elevated expression of HOTAIR promotes progression of breast cancer. In the current study we examined the expression and function of HOTAIR in MCF-7-TNR cells, a derivative of the luminal-like breast cancer cell line MCF-7 that acquired resistance to TNF-α-induced cell death. The expression of HOTAIR, markers of the luminal-like and basal-like subtypes, and growth were compared between MCF-7 and MCF-7-TNR cells. These variables were further assessed upon inhibition of HOTAIR, EZH2, p38 MAPK, and SRC kinase in MCF-7-TNR cells. When compared with MCF-7 cells, MCF-7-TNR cells exhibited an increase in the expression of HOTAIR, which correlated with characteristics of a luminal-like to basal-like transition as evidenced by dysregulated gene expression and accelerated growth. MCF-7-TNR cells exhibited reduced suppressive histone H3 lysine27 trimethylation on the HOTAIR promoter. Inhibition of HOTAIR and EZH2 attenuated the luminal-like to basal-like transition in terms of gene expression and growth in MCF-7-TNR cells. Inhibition of p38 and SRC diminished HOTAIR expression and the basal-like phenotype in MCF-7-TNR cells. HOTAIR was robustly expressed in the native basal-like breast cancer cells and inhibition of HOTAIR reduced the basal-like gene expression and growth. Our findings suggest HOTAIR-mediated regulation of gene expression and growth associated with the basal-like phenotype of breast cancer cells.

Keywords: EZH2; HOTAIR; breast cancer; lincRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Cell Line, Tumor
  • Enhancer of Zeste Homolog 2 Protein
  • Epigenesis, Genetic / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / genetics
  • Histones / genetics
  • Humans
  • MCF-7 Cells
  • Polycomb Repressive Complex 2 / genetics
  • RNA, Long Noncoding / genetics*
  • Tumor Necrosis Factor-alpha / genetics
  • p38 Mitogen-Activated Protein Kinases / genetics
  • src-Family Kinases / genetics


  • HOTAIR long untranslated RNA, human
  • Histones
  • RNA, Long Noncoding
  • Tumor Necrosis Factor-alpha
  • Histone Methyltransferases
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Histone-Lysine N-Methyltransferase
  • Polycomb Repressive Complex 2
  • src-Family Kinases
  • p38 Mitogen-Activated Protein Kinases