title: Brief report: The lincRNA Hotair is required for epithelial-to-mesenchymal transition and stemness maintenance of cancer cell lines.
abstract: 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.
authors.affiliation: 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.
authors.forename: Cleidson
authors.initials: C
authors.lastname: Pádua Alves
authors.forename: Aline Simoneti
authors.initials: AS
authors.lastname: Fonseca
authors.forename: Bruna Rodrigues
authors.initials: BR
authors.lastname: Muys
authors.forename: Rafaela
authors.initials: R
authors.lastname: de Barros E Lima Bueno
authors.forename: Matheus Carvalho
authors.initials: MC
authors.lastname: Bürger
authors.forename: Jorge E S
authors.initials: JE
authors.lastname: de Souza
authors.forename: Valeria
authors.initials: V
authors.lastname: Valente
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Zago
authors.forename: Wilson Araújo
authors.initials: WA
authors.lastname: Silva
mesh_terms: D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000502:physiology*; D062085:RNA, Long Noncoding / Q000235:genetics*; D014162:Transfection
chemical_list: C561566:HOTAIR long untranslated RNA, human; D062085:RNA, Long Noncoding
keywords: Cancer stem cell; Epithelial-to-mesenchymal transition; Hotair; LincRNA