Transcriptomics

Dataset Information

0

Epigenetic silencing of tumor suppressor miR-124 directly promotes STAT3 activation in Cutaneous T-cell Lymphoma


ABSTRACT: Increasing evidences support a potential role for the Signal Transducer and Activator of Transcription-3 (STAT3) as a tumor driver in cutaneous T-cell lymphoma (CTCL). However, the mechanisms leading to STAT3 pathway activation in CTCL and how STAT3 activation contributes to lymphomagenesis remains primarily not enough explored.  Recently, we found that miR-124, a known STAT3 regulator in cancer, is robustly silenced in Mycosis Fungoides (MF) tumor-stage and CTCL cell lines and we have herein studied whether deregulation of miR-124 contributes to activate STAT3 pathway in CTCL. Material and Methods: DNA methylation status of miR-124 and its expression levels in response to the DNA-demethylating agent azacitidine were evaluated in CTCL cell lines by pyrosequencing analysis. CTCL cell lines were transient transfected with a lentiviral vector encoding miR-124 and transfected cells were analyzed for phosphorylated STAT3 (P-STAT3) levels. The impact on STAT3 signaling was evaluated using expression microarray on CTCL cell lines in both conditions, miR-124 absent (malignant condition) versus miR-124 expressed (lentiviral transduction). Results: A significant promoter methylation and silencing of miR-124 in MF tumor samples and CTCL cell lines was detected. DNA methylation levels of miR-124 in CTCL cell lines were restored (and subsequently miR-124 were overexpressed) after DNA demethylation. Ectopic lentiviral expression of miR-124 downregulated STAT3 in the different CTCL cell lines. Genes differentially expressed regarding miR-124 regulation in CTCL cell lines indicated impact on known cell survival and function pathways and, particularly, intervention on miR-124 expression modulated different STAT3 pathway components. Conclusions: Our study deciphers a novel epigenetic mechanisms regulating STAT3 pathway in CTCL. This might contribute to a better understanding the molecular basis in CTCL development. Deregulation of STAT3 seems to have a major impact on cell survival in CTCL cell lines indicating the potential interest of targeting STAT3 with specific therapies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE130809 | GEO | 2020/12/31

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2018-08-20 | GSE112273 | GEO
2024-10-24 | GSE266862 | GEO
2022-10-06 | PXD035699 | Pride
2023-03-11 | PXD035626 | Pride
2021-12-07 | GSE181118 | GEO
| phs000913 | dbGaP
2015-03-31 | E-GEOD-59307 | biostudies-arrayexpress
2021-12-25 | GSE168508 | GEO
2024-10-13 | PXD042371 | Pride
| PRJNA213615 | ENA