BRD4 promotes the migration and invasion of bladder cancer cells through the Sonic hedgehog signaling pathway and enhances cisplatin resistance

Abstract

Platinum-based chemotherapy is a widely used strategy for bladder cancer (BCa) treatment. However, its clinical efficacy is affected by chemotherapy resistance via complex molecular mechanisms. Therefore, there is an urgent need to explore new targets for BCa therapy. Here, we showed that bromodomain-4 protein (BRD4) expression is upregulated in BCa tissues and cells. Inhibition of BRD4 attenuated the migration and invasion of BCa cells, which was rescued by the Sonic hedgehog (SHH) pathway activator recombinant human Sonic hedgehog peptide (rhSHH). We further found that cisplatin (DDP) suppressed the migration and invasion of BCa cells in vitro and inhibited tumor growth in vivo. However, overexpression of BRD4 weakened the pharmacological effects of DDP. In brief, our research revealed that BRD4 promotes migration and invasion by positively regulating the SHH pathway, drives DDP resistance in BCa, and is a novel therapeutic target for the treatment of BCa.