Dual epigenetic regulation of ERα36 expression in breast cancer cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue International Journal of Molecular Sciences Année : 2019

Dual epigenetic regulation of ERα36 expression in breast cancer cells

Résumé

Breast cancer remains the major cause of cancer-induced morbidity and mortality in women. Among the different molecular subtypes, luminal tumors yet considered of good prognosis often develop acquired resistance to endocrine therapy. Recently, misregulation of ERα36 was reported to play a crucial role in this process. High expression of this ERα isoform was associated to preneoplastic phenotype in mammary epithelial cells, disease progression, and enhanced resistance to therapeutic agents in breast tumors. In this study, we identified two mechanisms that could together contribute to ERα36 expression regulation. We first focused on hsa-miR-136-5p, an ERα36 3’UTR-targeting microRNA, the expression of which inversely correlated to the ERα36 one in breast cancer cells. Transfection of hsa-miR136-5p mimic in MCF-7 cells resulted in downregulation of ERα36. Moreover, the demethylating agent decitabine was able to stimulate hsa-miR-136-5p endogenous expression, thus indirectly decreasing ERα36 expression and counteracting tamoxifen-dependent stimulation. The methylation status of ERα36 promoter also directly modulated its expression level, as demonstrated after decitabine treatment of breast cancer cell and confirmed in a set of tumor samples. Taken together, these results open the way to a direct and an indirect ERα36 epigenetic modulation by decitabine as a promising clinical strategy to counteract acquired resistance to treatment and prevent relapse.

Domaines

Cancer
Fichier principal
Vignette du fichier
ijms-20-02637.pdf (1.87 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-02145413 , version 1 (25-10-2023)

Licence

Paternité

Identifiants

Citer

Charlène Thiébaut, Amand Chesnel, Jean-Louis Merlin, Maelle Chesnel, Agnès Leroux, et al.. Dual epigenetic regulation of ERα36 expression in breast cancer cells. International Journal of Molecular Sciences, 2019, 20 (11), pp.2637. ⟨10.3390/ijms20112637⟩. ⟨hal-02145413⟩
44 Consultations
11 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More