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-b1 resulted in increased Hotair expression and triggered the EMT program. Interestingly, ablation of Hotair expression by siRNA prevented the EMT program stimulated by TGF-b1, and also the colony-forming capacity of colon and breast cancer cells. Furthermore, we observed that the colon CSC subpopulation (CD133 1 /CD441 ) 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.

Large Intervening Non-Coding RNA HOTAIR Is an Indicator of Poor Prognosis and a Therapeutic Target in Human Cancers

“…In gastric cancer cells, the EMT may be triggered by HOTAIR through up-regulation of “ snail ” (a transcription factor involved in EMT). This is similar to the functional scenario of Figure 2( 2 ) [38]. Certainly, further demonstration is needed for supporting this viewpoint.…”

“…Padua Alves et al . [38] found that treatment with TGF-β1 increased HOTAIR expression and triggered the EMT program. Interestingly, ablation of HOTAIR expression by siRNA prevented the EMT program stimulated by TGF-β1, as well as the colony forming capacity of colon and breast cancer cells.…”

Evolution of Dermatofibrosarcoma Protuberans to DFSP-Derived Fibrosarcoma: An Event Marked by Epithelial–Mesenchymal Transition–like Process and 22q Loss

“…Moreover, 2 noncoding RNAs involved in the regulation of EZH2, H19, and HOTAIR (39-41) turned out to be among the RNAs most significantly upregulated in FS-DFSP. This finding suggests that overexpression of H19 and HOTAIR, together with let-7 downregulation, all concur to induce EZH2 and, in turn, chromatin remodeling and mesenchymal transdifferentiation in FS-DFSP (19,(39)(40)(41). A role for epigenetic reprogramming in fibrosarcomatous transformation was also supported by the finding that 66 genes enriched in FS-DFSP versus DFSP are reported to undergo epigenetic regulation (11), and recent evidence is consistent with the involvement of chromatin remodeling in translocation-associated sarcomas (42).…”

LncRNA HOTAIR: A master regulator of chromatin dynamics and cancer

“…evaluated the roles played by HOTAIR in epithelial-to-mesenchymal transition (EMT) and also in the maintenance of cancer stem cells (CSCs. Their study demonstrated that treatment with TGFβ1 (Transforming growth factor β1) induces HOTAIR levels and triggers EMT [129]. However, depletion of HOTAIR did not trigger TGFβ1 stimulated EMT program and also alleviated the colony-forming capacity of colon and breast cancer cells.…”