Nuclear Receptors in Bladder Cancer: Insights into miRNA-Mediated Regulation and Potential Therapeutic Implications

TL;DR

This review explores how nuclear receptors and microRNAs interact in bladder cancer, offering new insights into potential treatments and biomarkers.

Contribution

The paper provides an integrated overview of miRNA–nuclear receptor interactions and their therapeutic implications in bladder cancer.

Findings

miRNAs regulate nuclear receptor expression and function in bladder cancer.

Nuclear receptors influence miRNA biogenesis, forming feedback loops that affect tumor behavior.

Targeting miRNA–nuclear receptor networks shows promise for improving bladder cancer treatment.

Abstract

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression and are involved in diverse physiological and pathological processes, including carcinogenesis. In bladder cancer (BCa), dysregulation of NR signaling pathways has been linked to tumor initiation, progression, therapy resistance, and immune evasion. Recent evidence highlights the intricate crosstalk between NRs and microRNAs (miRNAs), which are small non-coding RNAs that posttranscriptionally modulate gene expression. This review provides an integrated overview of the molecular interactions between key NRs and miRNAs in BCa. We investigated how miRNAs regulate NR expression and function and, conversely, how NRs influence miRNA biogenesis, thereby forming regulatory feedback loops that shape tumor behavior. Specific miRNA–NR interactions affecting epithelial-to-mesenchymal transition, metabolic reprogramming, angiogenesis, and chemoresistance are discussed in detail. Additionally, we highlight therapeutic strategies targeting NR–miRNA networks, including selective NR modulators, miRNA mimics and inhibitors, as well as RNA-based combinatorial approaches focusing on their utility as diagnostic biomarkers and personalized treatment targets. Understanding the molecular complexity of NR–miRNA regulation in BCa may open new avenues for improving therapeutic outcomes and advancing precision oncology in urological cancers.

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