Epigenetic Silencing of Tumor Suppressor miR-124 Directly Supports STAT3 Activation in Cutaneous T-Cell Lymphoma
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Identificadores
URI: http://hdl.handle.net/20.500.11940/16506
PMID: 33333886
DOI: 10.3390/cells9122692
ISSN: 2073-4409
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Fecha de publicación
2020Título de revista
Cells
Tipo de contenido
Journal Article
DeCS
neoplasias cutáneas | microARN | linfoma | línea celular | factor de transcripción STAT3 | humanos | cinasas Janus | regulación de la expresión génica | metilación del ADNMeSH
Skin Neoplasms | MicroRNAs | Cell Line | Humans | Janus Kinases | Lymphoma | DNA Methylation | Gene Expression Regulation | STAT3 Transcription FactorResumen
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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