Brief Report: The lincRNA Hotair Is Required for Epithelial-to-Mesenchymal Transition and Stemness Maintenance of Cancer Cell Lines

Author(s)

Alves, Cleidson Padua ^{[1, 2, 3, 4]} ; Fonseca, Aline Simoneti ^{[1, 2, 3]} ; Muys, Bruna Rodrigues ^{[1, 2, 3]} ; Bueno, Rafaela de Barros e Lima ^{[1, 2, 3]} ; Buerger, Matheus Carvalho ^{[5, 1, 2, 3, 4]} ; de Souza, Jorge E. S. ^{[5, 1, 2, 3, 4]} ; Valente, Valeria ^{[1, 3, 4, 6]} ; Zago, Marco Antonio ^{[1, 3, 7]} ; Silva, Jr., Wilson Araujo ^{[1, 2, 3, 4]}

Affiliation

^[1] Natl Inst Sci & Technol Stem Cell & Cell Therapy, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Genet, Ribeirao Preto Med Sch, Sao Paulo - Brazil

^[3] Ctr Cell Based Therapy, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Ctr Integrat Syst Biolo CISBi, NAP, BR-09500900 Sao Paulo - Brazil

^[5] Inst Bioinformat & Biotechnol 2bio, Sao Paulo - Brazil

^[6] Univ Estadual Paulista, Fac Pharmaceut Sci Araraquara, Sao Paulo - Brazil

^[7] Univ Sao Paulo, Dept Internal Med, Ribeirao Preto Med Sch, Sao Paulo - Brazil

• Document type: Journal article
• Source: Stem Cells; v. 31, n. 12, p. 2827-2832, DEC 2013.
• Web of Science Citations: 115

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-1 resulted in increased Hotair expression and triggered the EMT program. Interestingly, ablation of Hotair expression by siRNA prevented the EMT program stimulated by TGF-1, 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. (AU)

• FAPESP's process: 98/14247-6 - Center for Research on Cell-Based Therapy
• Grantee: Marco Antonio Zago
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC