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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7765332 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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