BET Bromodomain Inhibition Reverses CDK4/6 Inhibitor Resistance in Estrogen Receptor-Positive Breast Cancer via Induction of miR-34a-5p.

ABSTRACT:

Purpose

CDK6 overexpression is one critical determinant of acquired CDK4/6 inhibitor resistance. Because BRD4 is recruited to the CDK6 promoter, we investigated the potential of bromodomain and extraterminal domain (BET) inhibition to reverse CDK4/6 inhibitor resistance.

Experimental design

Cell viability and survival assays and cell line xenografts were used to evaluate BET inhibition in palbociclib-resistant breast cancer cells. Vehicle- and BET inhibitor-treated cells were subjected to RNA sequencing. CDK6 promoter activity was assessed with luciferase assays, and the miRPathDB version 2.0 database was used to identify potential miRNA mediating the effects of BET inhibition. Experiments were conducted to determine whether continued palbociclib treatment is essential for B

SUBMITTER: Liu R 

PROVIDER: S-EPMC12596151 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature