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

Yan Zhuang, Hong T. Nguyen, Matthew E. Burow, Ying Zhuo, Samir S. El-Dahr, Xiao Yao, Subing Cao, Erik K. Flemington, Kenneth P. Nephew, Fang Fang, Bridgette Collins-Burow, Lyndsay V. Rhodes, Qiang Yu, Janarthanan Jayawickramarajah, Bin Shan

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1656-1667
Number of pages12
JournalMolecular Carcinogenesis
Volume54
Issue number12
DOIs
StatePublished - Dec 2015

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Keywords

  • Breast cancer
  • EZH2
  • HOTAIR
  • LincRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Zhuang, Y., Nguyen, H. T., Burow, M. E., Zhuo, Y., El-Dahr, S. S., Yao, X., Cao, S., Flemington, E. K., Nephew, K. P., Fang, F., Collins-Burow, B., Rhodes, L. V., Yu, Q., Jayawickramarajah, J., & Shan, B. (2015). Elevated expression of long intergenic non-coding RNA HOTAIR in a basal-like variant of MCF-7 breast cancer cells. Molecular Carcinogenesis, 54(12), 1656-1667. https://doi.org/10.1002/mc.22237