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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MDPI AG
2020-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/12/2692 |
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| author | Lidia García-Colmenero Jéssica González Juan Sandoval Yolanda Guillén Angel Diaz-Lagares Evelyn Andrades Arnau Iglesias Lara Nonell Ramon Maria Pujol Anna Bigas Lluís Espinosa Fernando Gallardo |
| author_facet | Lidia García-Colmenero Jéssica González Juan Sandoval Yolanda Guillén Angel Diaz-Lagares Evelyn Andrades Arnau Iglesias Lara Nonell Ramon Maria Pujol Anna Bigas Lluís Espinosa Fernando Gallardo |
| author_sort | Lidia García-Colmenero |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T14:04:21Z |
| format | Article |
| id | doaj.art-d6329ff60193474e860ed2d3e0c2f144 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T14:04:21Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-d6329ff60193474e860ed2d3e0c2f1442023-11-21T00:53:08ZengMDPI AGCells2073-44092020-12-01912269210.3390/cells9122692Epigenetic Silencing of Tumor Suppressor miR-124 Directly Supports STAT3 Activation in Cutaneous T-Cell LymphomaLidia García-Colmenero0Jéssica González1Juan Sandoval2Yolanda Guillén3Angel Diaz-Lagares4Evelyn Andrades5Arnau Iglesias6Lara Nonell7Ramon Maria Pujol8Anna Bigas9Lluís Espinosa10Fernando Gallardo11Department of Dermatology, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Autònoma Barcelona, Carrer del Dr. Aiguader, 88, 08003 Barcelona, SpainCancer Research Program Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, SpainEpigenomics Unit, IIS, La Fe, 46026 Valencia, SpainStem Cells and Cancer Research Laboratory-IMIM, CIBERONC, 08003 Barcelona, SpainCancer Epigenomics, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), CIBERONC, 15706 Santiago de Compostela, SpainDepartment of Dermatology, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Autònoma Barcelona, Carrer del Dr. Aiguader, 88, 08003 Barcelona, SpainCancer Research Program Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, SpainMicroarray Department-IMIM, 08003 Barcelona, SpainDepartment of Dermatology, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Autònoma Barcelona, Carrer del Dr. Aiguader, 88, 08003 Barcelona, SpainStem Cells and Cancer Research Laboratory-IMIM, CIBERONC, 08003 Barcelona, SpainStem Cells and Cancer Research Laboratory-IMIM, CIBERONC, 08003 Barcelona, SpainDepartment of Dermatology, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Autònoma Barcelona, Carrer del Dr. Aiguader, 88, 08003 Barcelona, SpainIncreasing 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.https://www.mdpi.com/2073-4409/9/12/2692cutaneous T-cell lymphomamycosis fungoidesSézary syndromeSTAT3 (signal transducer and activator of transcription-3)JAK/STAT (janus kinase/signal transducer and activator of transcription)miR-124 |
| spellingShingle | Lidia García-Colmenero Jéssica González Juan Sandoval Yolanda Guillén Angel Diaz-Lagares Evelyn Andrades Arnau Iglesias Lara Nonell Ramon Maria Pujol Anna Bigas Lluís Espinosa Fernando Gallardo Epigenetic Silencing of Tumor Suppressor miR-124 Directly Supports STAT3 Activation in Cutaneous T-Cell Lymphoma Cells cutaneous T-cell lymphoma mycosis fungoides Sézary syndrome STAT3 (signal transducer and activator of transcription-3) JAK/STAT (janus kinase/signal transducer and activator of transcription) miR-124 |
| 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 | cutaneous T-cell lymphoma mycosis fungoides Sézary syndrome STAT3 (signal transducer and activator of transcription-3) JAK/STAT (janus kinase/signal transducer and activator of transcription) miR-124 |
| url | https://www.mdpi.com/2073-4409/9/12/2692 |
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