Brief report: The lincRNA Hotair is required for epithelial-to-mesenchymal transition and stemness maintenance of cancer cell lines.

Autor: Pádua Alves C; Department of Genetics and, Ribeirão Preto Medical School University of São Paulo, São Paulo, Brazil; National Institute of Science and Technology in Stem Cell and Cell Therapy and Center For Cell Based Therapy, Ribeirao Preto, São Paulo, Brazil; Center for Integrative Systems Biology-CISBi, NAP/USP, Ribeirao Preto, São Paulo, Brazil., Fonseca AS, Muys BR, de Barros E Lima Bueno R, Bürger MC, de Souza JE, Valente V, Zago MA, Silva WA Jr
Jazyk: angličtina
Zdroj: Stem cells (Dayton, Ohio) [Stem Cells] 2013 Dec; Vol. 31 (12), pp. 2827-32.
DOI: 10.1002/stem.1547
Abstrakt: Hotair is a member of the recently described class of noncoding RNAs called lincRNA (large intergenic noncoding RNA). Various studies suggest that Hotair acts regulating epigenetic states by recruiting chromatin-modifying complexes to specific target sequences that ultimately leads to suppression of several genes. Although Hotair has been associated with metastasis and poor prognosis in different tumor types, a deep characterization of its functions in cancer is still needed. Here, we investigated the role of Hotair in the scenario of epithelial-to-mesenchymal transition (EMT) and in the arising and maintenance of cancer stem cells (CSCs). We found that treatment with TGF-β1 resulted in increased Hotair expression and triggered the EMT program. Interestingly, ablation of Hotair expression by siRNA prevented the EMT program stimulated by TGF-β1, and also the colony-forming capacity of colon and breast cancer cells. Furthermore, we observed that the colon CSC subpopulation (CD133(+)/CD44(+)) presents much higher levels of Hotair when compared with the non-stem cell subpopulation. These results indicate that Hotair acts as a key regulator that controls the multiple signaling mechanisms involved in EMT. Altogether, our data suggest that the role of Hotair in tumorigenesis occurs through EMT triggering and stemness acquisition.
(© AlphaMed Press.)
Databáze: MEDLINE
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