Long non-coding RNAs (LncRNA) regulated by transforming growth factor (TGF) β: LncRNA-hit-mediated TGFβ-induced epithelial to mesenchymal transition in mammary epithelia.

Autor:	Richards EJ; From the Departments of Molecular Oncology., Zhang G; the Zhejiang Cancer Hospital & Zhejiang Cancer Research Institute, Zhejiang 310022, China., Li ZP; the Zhejiang Cancer Hospital & Zhejiang Cancer Research Institute, Zhejiang 310022, China., Permuth-Wey J; Cancer Epidemiology, and., Challa S; From the Departments of Molecular Oncology., Li Y; From the Departments of Molecular Oncology., Kong W; From the Departments of Molecular Oncology., Dan S; the Zhejiang Cancer Hospital & Zhejiang Cancer Research Institute, Zhejiang 310022, China., Bui MM; Anatomic Pathology, Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612 and., Coppola D; Anatomic Pathology, Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612 and., Mao WM; the Zhejiang Cancer Hospital & Zhejiang Cancer Research Institute, Zhejiang 310022, China., Sellers TA; Cancer Epidemiology, and., Cheng JQ; From the Departments of Molecular Oncology, jin.cheng@moffitt.org.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2015 Mar 13; Vol. 290 (11), pp. 6857-67. Date of Electronic Publication: 2015 Jan 20.
DOI:	10.1074/jbc.M114.610915
Abstrakt:	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. (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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