Epigenetic silencing of tumor suppressor miR-124 directly supports STAT3 activation in cutaneous T-Cell lymphoma

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• dc.contributor.author García-Colmenero, Lidia
• dc.contributor.author González Miranda, Jessica
• dc.contributor.author Sandoval, Juan
• dc.contributor.author Guillén, Yolanda
• dc.contributor.author Diaz-Lagares, Angel
• dc.contributor.author Andrades, Evelyn
• dc.contributor.author Iglesias, Arnau
• dc.contributor.author Nonell Mazelon, Lara, 1972-
• dc.contributor.author Pujol Vallverdú, Ramon Maria
• dc.contributor.author Bigas Salvans, Anna
• dc.contributor.author Espinosa Blay, Lluís
• dc.contributor.author Gallardo Hernández, Fernando
• dc.date.accessioned 2021-06-10T07:06:24Z
• dc.date.available 2021-06-10T07:06:24Z
• dc.date.issued 2020
• dc.description.abstract Increasing evidence supports a potential role for STAT3 as a tumor driver in cutaneous T-cell lymphomas (CTCL). The mechanisms leading to STAT3 activation are not fully understood; however, we recently found that miR-124, a known STAT3 regulator, is robustly silenced in MF tumor-stage and CTCL cells. Objective: We studied here whether deregulation of miR-124 contributes to STAT3 pathway activation in CTCL. Methods: We measured the effect of ectopic mir-124 expression in active phosphorylated STAT3 (p-STAT3) levels and evaluated the transcriptional impact of miR-124-dependent STAT3 pathway regulation by expression microarray analysis. Results: We found that ectopic expression of miR-124 results in massive downregulation of activated STAT3 in different CTCL lines, which resulted in a significant alteration of genetic signatures related with gene transcription and proliferation such as MYC and E2F. Conclusions: Our study highlights the importance of the miR-124/STAT3 axis in CTCL and demonstrates that the STAT3 pathway is regulated through epigenetic mechanisms in these cells. Since deregulated STAT3 signaling has a major impact on CTCL initiation and progression, a better understanding of the molecular basis of the miR-124/STAT3 axis may provide useful information for future personalized therapies.
• dc.format.mimetype application/pdf
• dc.identifier.citation García-Colmenero L, González J, Sandoval J, Guillén Y, Diaz-Lagares A, Andrades E, et al. Epigenetic silencing of tumor suppressor miR-124 directly supports STAT3 activation in cutaneous T-Cell lymphoma. Cells. 2020 Dec 15; 9(12): 2692. DOI: 10.3390/cells9122692
• dc.identifier.doi http://dx.doi.org/10.3390/cells9122692
• dc.identifier.issn 2073-4409
• dc.identifier.uri http://hdl.handle.net/10230/47825
• dc.language.iso eng
• dc.publisher MDPI
• dc.rights Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword JAK/STAT (janus kinase/signal transducer and activator of transcription)
• dc.subject.keyword STAT3 (signal transducer and activator of transcription-3)
• dc.subject.keyword Sézary syndrome
• dc.subject.keyword utaneous T-cell lymphoma
• dc.subject.keyword miR-124
• dc.subject.keyword Mycosis fungoides
• dc.title Epigenetic silencing of tumor suppressor miR-124 directly supports STAT3 activation in cutaneous T-Cell lymphoma
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion