title: Long non-coding RNAs (LncRNA) regulated by transforming growth factor (TGF) β: LncRNA-hit-mediated TGFβ-induced epithelial to mesenchymal transition in mammary epithelia.
abstract: Long noncoding RNAs (lncRNAs) are emerging as key regulators in various biological processes. Epithelial-to-mesenchymal transition (EMT) is a developmental process hijacked by tumor cells to depart from the primary tumor site, invade surrounding tissue, and establish distant metastases. Transforming growth factor β (TGFβ) signaling has been shown to be a major inducer of EMT and to facilitate breast cancer metastasis. However, the role of lncRNAs in this process remains largely unknown. Here we report a genome-wide lncRNA profile in mouse mammary epithelial NMuMG cells upon TGFβ induction of EMT. Among 10,802 lncRNAs profiled, over 600 were up-regulated and down-regulated during the EMT, respectively. Furthermore, we identify that lncRNA-HIT (HOXA transcript induced by TGFβ) mediates TGFβ function, i.e. depletion of lncRNA-HIT inhibits TGFβ-induced migration, invasion, and EMT in NMuMG. LncRNA-HIT is also significantly elevated in the highly metastatic 4T1 cells. Knockdown of lncRNA-HIT in 4T1 results in decrease of cell migration, invasion, tumor growth, and metastasis. E-cadherin was identified as a major target of lncRNA-HIT. Moreover, lncRNA-HIT is conserved in humans and elevated expression associates with more invasive human primary breast carcinoma. Collectively, these data suggest that a subset of lncRNAs such as lncRNA-HIT play a significant role in regulation of EMT and breast cancer invasion and metastasis, and could be potential therapeutic targets in breast cancers.
authors.affiliation: From the Departments of Molecular Oncology.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Richards
authors.affiliation: the Zhejiang Cancer Hospital & Zhejiang Cancer Research Institute, Zhejiang 310022, China.
authors.forename: Gu
authors.initials: G
authors.lastname: Zhang
authors.affiliation: the Zhejiang Cancer Hospital & Zhejiang Cancer Research Institute, Zhejiang 310022, China.
authors.forename: Zhu-Peng
authors.initials: ZP
authors.lastname: Li
authors.affiliation: Cancer Epidemiology, and.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Permuth-Wey
authors.affiliation: From the Departments of Molecular Oncology.
authors.forename: Sridevi
authors.initials: S
authors.lastname: Challa
authors.affiliation: From the Departments of Molecular Oncology.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: From the Departments of Molecular Oncology.
authors.forename: William
authors.initials: W
authors.lastname: Kong
authors.affiliation: the Zhejiang Cancer Hospital & Zhejiang Cancer Research Institute, Zhejiang 310022, China.
authors.forename: Su
authors.initials: S
authors.lastname: Dan
authors.affiliation: Anatomic Pathology, Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612 and.
authors.forename: Marilyn M
authors.initials: MM
authors.lastname: Bui
authors.affiliation: Anatomic Pathology, Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612 and.
authors.forename: Domenico
authors.initials: D
authors.lastname: Coppola
authors.affiliation: the Zhejiang Cancer Hospital & Zhejiang Cancer Research Institute, Zhejiang 310022, China.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Mao
authors.affiliation: Cancer Epidemiology, and.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Sellers
authors.affiliation: From the Departments of Molecular Oncology, jin.cheng@moffitt.org.
authors.forename: Jin Q
authors.initials: JQ
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D062085:RNA, Long Noncoding; D016212:Transforming Growth Factor beta
keywords: Breast Cancer; Epithelial-esenchymal Transition (EMT); Long Noncoding RNA (Long ncRNA, LncRNA); Metastasis; Transforming Growth Factor β (TGF-β)