The regulatory mechanism and clinical significance of RNA editing in prostate cancer.

Prostate cancer (PCa) is one of the most common malignancies in men and remains particularly challenging as it progresses to the castration-resistant stage. Increasing evidence indicates that dysregulated RNA editing plays an active role in PCa progression and resistance to therapy. Among these modifications, adenosine-to-inosine editing catalyzed by adenosine deaminase acting on RNA 1 (ADAR1) alters transcripts, such as androgen receptor (AR) and antizyme inhibitor 1, promoting androgen-independent growth, metastasis, and immune evasion. Conversely, cytidine-to-uridine editing mediated by apolipoprotein B mRNA editing catalytic polypeptide-like 3 (APOBEC3) enzymes contributes to genomic instability. For example, APOBEC3B induces mutagenesis and resistance to AR-targeted therapy, and APOBEC3C functions as a context-dependent tumor suppressor that is transcriptionally repressed by the AR in advanced disease. Clinically, RNA editing signatures, including APOBEC3C expression levels, have shown promise as biomarkers for risk stratification, disease monitoring, and prognosis. Therapeutically, inhibition of ADAR1 or APOBEC3B, restoration of APOBEC3C activity, and site-specific corrective RNA editing using the CRISPR-ADAR2 platform represent emerging precision strategies. Ongoing development of small-molecule inhibitors, oligonucleotide-based modulators, and liquid biopsy-based detection methods further highlights the translational relevance of RNA editing in PCa. Future research should focus on improving editing specificity, minimizing off-target effects, and validating these biomarkers and therapeutic targets in clinical settings to fully realize the diagnostic and therapeutic potential of RNA editing in the precise management of prostate cancer.