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

肿瘤抑制因子 miR-124 的表观遗传沉默直接支持皮肤 T 细胞淋巴瘤中的 STAT3 激活

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作者: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

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.

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.

Objective

We studied here whether deregulation of miR-124 contributes to STAT3 pathway activation in CTCL.

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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