miR-205 Regulates Tamoxifen Resistance by Targeting Estrogen Receptor Coactivator MED1 in Human Breast Cancer DOI Open Access
Bin Ouyang, M. Bi, Mahendra Jadhao

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(23), P. 3992 - 3992

Published: Nov. 28, 2024

Background/Objectives: Estrogen receptor-α coactivator MED1 is overexpressed in 40–60% of human breast cancers, and its high expression correlates with poor disease-free survival patients undergoing anti-estrogen therapy. However, the molecular mechanism underlying upregulation activation cancer treatment resistance remains elusive. Methods: miRNA mRNA analysis was performed using NCBI GEO database. targeting impact on therapy evaluated control tamoxifen-resistant cell lines by miR-205 overexpression inhibition. Immunoblotting, chromatin immunoprecipitation, luciferase reporter assays were used to understand MED1-mediated tamoxifen resistance. Mice xenograft models validate efficacy mechanisms vivo. Results: found directly target suppress through bioinformatic analyses experimental validations. An inverse correlation observed MED1/low miR-205, indicative prognosis long-term treatment. Furthermore, depletion cells overexpressing MED1. The restoration attenuated re-sensitized both vitro Interestingly, miR205 also another key regulatory gene, HER3, which drives PI3K/Akt signaling phosphorylation. Importantly, we ER gene transcription promoter cofactor recruitment can be reversed induced expression. Conclusions: Altogether, functions as a negative regulator affecting regulation HER3-PI3K/Akt-MED1 axis resistance, could serve potential therapeutic regime overcome

Language: Английский

miR-205 Regulates Tamoxifen Resistance by Targeting Estrogen Receptor Coactivator MED1 in Human Breast Cancer DOI Open Access
Bin Ouyang, M. Bi, Mahendra Jadhao

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(23), P. 3992 - 3992

Published: Nov. 28, 2024

Background/Objectives: Estrogen receptor-α coactivator MED1 is overexpressed in 40–60% of human breast cancers, and its high expression correlates with poor disease-free survival patients undergoing anti-estrogen therapy. However, the molecular mechanism underlying upregulation activation cancer treatment resistance remains elusive. Methods: miRNA mRNA analysis was performed using NCBI GEO database. targeting impact on therapy evaluated control tamoxifen-resistant cell lines by miR-205 overexpression inhibition. Immunoblotting, chromatin immunoprecipitation, luciferase reporter assays were used to understand MED1-mediated tamoxifen resistance. Mice xenograft models validate efficacy mechanisms vivo. Results: found directly target suppress through bioinformatic analyses experimental validations. An inverse correlation observed MED1/low miR-205, indicative prognosis long-term treatment. Furthermore, depletion cells overexpressing MED1. The restoration attenuated re-sensitized both vitro Interestingly, miR205 also another key regulatory gene, HER3, which drives PI3K/Akt signaling phosphorylation. Importantly, we ER gene transcription promoter cofactor recruitment can be reversed induced expression. Conclusions: Altogether, functions as a negative regulator affecting regulation HER3-PI3K/Akt-MED1 axis resistance, could serve potential therapeutic regime overcome

Language: Английский

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