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Epigenetic Silencing of Tumor Suppressor miR-124 Directly Supports STAT3 Activation in Cutaneous T-Cell Lymphoma

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...

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Autores principales: García-Colmenero, Lidia, González, Jéssica, Sandoval, Juan, Guillén, Yolanda, Diaz-Lagares, Angel, Andrades, Evelyn, Iglesias, Arnau, Nonell, Lara, Pujol, Ramon Maria, Bigas, Anna, Espinosa, Lluís, Gallardo, Fernando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765332/
https://www.ncbi.nlm.nih.gov/pubmed/33333886
http://dx.doi.org/10.3390/cells9122692
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author García-Colmenero, Lidia
González, Jéssica
Sandoval, Juan
Guillén, Yolanda
Diaz-Lagares, Angel
Andrades, Evelyn
Iglesias, Arnau
Nonell, Lara
Pujol, Ramon Maria
Bigas, Anna
Espinosa, Lluís
Gallardo, Fernando
author_facet García-Colmenero, Lidia
González, Jéssica
Sandoval, Juan
Guillén, Yolanda
Diaz-Lagares, Angel
Andrades, Evelyn
Iglesias, Arnau
Nonell, Lara
Pujol, Ramon Maria
Bigas, Anna
Espinosa, Lluís
Gallardo, Fernando
author_sort García-Colmenero, Lidia
collection PubMed
description 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.
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spelling pubmed-77653322020-12-27 Epigenetic Silencing of Tumor Suppressor miR-124 Directly Supports STAT3 Activation in Cutaneous T-Cell Lymphoma García-Colmenero, Lidia González, Jéssica Sandoval, Juan Guillén, Yolanda Diaz-Lagares, Angel Andrades, Evelyn Iglesias, Arnau Nonell, Lara Pujol, Ramon Maria Bigas, Anna Espinosa, Lluís Gallardo, Fernando Cells Article 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. MDPI 2020-12-15 /pmc/articles/PMC7765332/ /pubmed/33333886 http://dx.doi.org/10.3390/cells9122692 Text en © 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/).
spellingShingle Article
García-Colmenero, Lidia
González, Jéssica
Sandoval, Juan
Guillén, Yolanda
Diaz-Lagares, Angel
Andrades, Evelyn
Iglesias, Arnau
Nonell, Lara
Pujol, Ramon Maria
Bigas, Anna
Espinosa, Lluís
Gallardo, Fernando
Epigenetic Silencing of Tumor Suppressor miR-124 Directly Supports STAT3 Activation in Cutaneous T-Cell Lymphoma
title Epigenetic Silencing of Tumor Suppressor miR-124 Directly Supports STAT3 Activation in Cutaneous T-Cell Lymphoma
title_full Epigenetic Silencing of Tumor Suppressor miR-124 Directly Supports STAT3 Activation in Cutaneous T-Cell Lymphoma
title_fullStr Epigenetic Silencing of Tumor Suppressor miR-124 Directly Supports STAT3 Activation in Cutaneous T-Cell Lymphoma
title_full_unstemmed Epigenetic Silencing of Tumor Suppressor miR-124 Directly Supports STAT3 Activation in Cutaneous T-Cell Lymphoma
title_short Epigenetic Silencing of Tumor Suppressor miR-124 Directly Supports STAT3 Activation in Cutaneous T-Cell Lymphoma
title_sort epigenetic silencing of tumor suppressor mir-124 directly supports stat3 activation in cutaneous t-cell lymphoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765332/
https://www.ncbi.nlm.nih.gov/pubmed/33333886
http://dx.doi.org/10.3390/cells9122692
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