Androgen receptor mRNA (AR mRNA)

Androgen receptor (AR) mRNA is the messenger RNA transcript encoded by the AR gene, serving as the template for the synthesis of the androgen receptor protein. The AR protein is a nuclear transcription factor that mediates the biological effects of androgens like testosterone and dihydrotestosterone, playing a pivotal role in male sexual development and the progression of prostate cancer (PubMed: 25162882). In advanced stages of disease, such as castration-resistant prostate cancer (CRPC), the AR pathway often remains active through mechanisms like AR gene amplification, mutations, or the expression of truncated splice variants like AR-V7 that lack a ligand-binding domain (PubMed: 25188503). Targeting the AR mRNA using antisense oligonucleotides (ASOs) or RNA interference (RNAi) allows for the depletion of all AR protein isoforms, including those resistant to conventional antagonists (ClinicalTrials.gov: NCT03300505). This therapeutic strategy aims to bypass traditional resistance mechanisms by preventing the production of the receptor at the pre-translational level. Clinical candidates like AZD5312 have been investigated for their ability to reduce AR expression and inhibit tumor growth in patients with metastatic CRPC (PubMed: 32435030). Beyond oncology, the AR mRNA is also relevant in neuromuscular disorders like spinal and bulbar muscular atrophy, where CAG repeat expansions in the transcript lead to proteotoxicity (PubMed: 21163910).

Other names

Androgen receptor transcriptNR3C4 mRNAAndrogen receptor messenger RNANuclear receptor subfamily 3 group C member 4 mRNADihydrotestosterone receptor mRNA

Antisense oligonucleotides (ASOs) bind to the AR mRNA through Watson-Crick base pairing, which triggers the recruitment of RNase H to cleave the RNA-DNA heteroduplex, thereby degrading the mRNA and preventing the translation of the androgen receptor protein (PubMed: 32435030).