title: Elevated expression of long intergenic non-coding RNA HOTAIR in a basal-like variant of MCF-7 breast cancer cells.
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.
authors.affiliation: Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Hong T
authors.initials: HT
authors.lastname: Nguyen
authors.affiliation: Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Burow
authors.affiliation: Kadlec Regional Medical Center, Richland, Washington.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhuo
authors.affiliation: Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Samir S
authors.initials: SS
authors.lastname: El-Dahr
authors.affiliation: Kadlec Regional Medical Center, Richland, Washington.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Subing
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Erik K
authors.initials: EK
authors.lastname: Flemington
authors.affiliation: Department of Medical Sciences, Indiana University School of Medicine, Bloomington, Indiana.
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Nephew
authors.affiliation: Department of Medical Sciences, Indiana University School of Medicine, Bloomington, Indiana.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Bridgette
authors.initials: B
authors.lastname: Collins-Burow
authors.affiliation: Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Lyndsay V
authors.initials: LV
authors.lastname: Rhodes
authors.affiliation: Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Chemistry, Tulane University, New Orleans, Louisiana.
authors.forename: Janarthanan
authors.initials: J
authors.lastname: Jayawickramarajah
authors.affiliation: Washington State University at Spokane, Spokane, Washington.
authors.forename: Bin
authors.initials: B
authors.lastname: Shan
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics; D006657:Histones / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D063151:Polycomb Repressive Complex 2 / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics; D019061:src-Family Kinases / Q000235:genetics
chemical_list: C561566:HOTAIR long untranslated RNA, human; D006657:Histones; D062085:RNA, Long Noncoding; D014409:Tumor Necrosis Factor-alpha; D000076983:Histone Methyltransferases; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; D019061:src-Family Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: EZH2; HOTAIR; breast cancer; lincRNA