Evaluating Gliclazide as a Safer Alternative Treatment for Castration- Resistant Prostate Cancer via lncRNA-Mediated Androgen Receptor Interactions

Prostate cancer, the second most prevalent type of cancer globally, necessitates focused efforts in both diagnosis and treatment. While numerous molecules are implicated in the progression of metastatic castration-resistant prostate cancer (CRPC), the regulation of CRPC remains unknown. This study investigates this transition through bioinformatic analysis, revealing critical interactions between testosterone and androgen receptors facilitated by long non-coding RNAs (lncRNAs) PRNCR1 and PCGEM1. These lncRNAs are shown to play a significant role in the progression to CRPC, operating independently of testosterone regulation. Furthermore, the study evaluates the repurposing of anti-diabetic drugs for prostate cancer treatment. The in silico analysis demonstrated a link between testosterone and the androgen receptor through the interaction of PRNCR1 and PCGEM1. Among the 15 anti-diabetic drugs analyzed, Gliclazide was identified as the most promising candidate, effectively disrupting the critical protein interactions mediated by PRNCR1 and PCGEM1. These findings not only elucidate the molecular mechanisms underlying CRPC progression but also propose a novel therapeutic approach by repurposing anti-diabetic drugs for prostate cancer treatment. This study provides new insights into the biology of CRPC and suggests a relatively less harmful treatment for more effective treatments of patients as an alternative to conventional therapies.