Zhuang, YanNguyen, Hong T.Burow, Matthew E.Zhuo, YingEl-Dahr, Samir S.Yao, XiaoCao, SubingFlemington, Erik K.Nephew, Kenneth P.Fang, FangCollins-Burow, BridgetteRhodes, Lyndsay V.Yu, QiangJayawickramarajah, JanarthananShan, Bin2017-06-122017-06-122015-12Zhuang, Y., Nguyen, H. T., Burow, M. E., Zhuo, Y., El-Dahr, S. S., Yao, X., … 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. http://doi.org/10.1002/mc.22237https://hdl.handle.net/1805/12959Epigenetic 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.en-USPublisher PolicyEZH2HOTAIRBreast cancerLincRNAArticle