A novel AR translational regulator lncRNA LBCS inhibits castration resistance of prostate cancer

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Prostate cancer (PCa) progression to castration resistance (CRPC) is a major cause of mortality.
• Androgen Receptor (AR) signaling is central to CRPC development, necessitating research into AR activation mechanisms under low androgen conditions.
• Understanding these mechanisms is critical for developing novel CRPC treatments.

Purpose of the Study:

• To identify long non-coding RNAs (lncRNAs) associated with CRPC.
• To investigate the role and mechanism of a specific lncRNA, lnc-LBCS, in CRPC progression.
• To explore the potential of targeting the LBCS-hnRNPK-AR axis for CRPC therapy.

Main Methods:

• Transcriptome microarray analysis to identify CRPC-associated lncRNAs.
• Expression analysis and clinical feature correlation of lnc-LBCS in independent patient cohorts.
• In vitro gain and loss of function assays to determine the functional role of lnc-LBCS in prostate cancer cells.

Main Results:

• Lnc-LBCS expression was found to be downregulated in CRPC cell lines and tissues.
• Lower LBCS expression correlated with higher Gleason Score, advanced T stage, and poorer PCa prognosis.
• LBCS overexpression inhibited castration resistance traits, while LBCS knockdown promoted them by elevating AR protein translation via interaction with hnRNPK.

Conclusions:

• Lnc-LBCS acts as a novel AR translational regulator, suppressing castration resistance in prostate cancer.
• The interaction between LBCS and hnRNPK suppresses AR translation, offering a new insight into lncRNA-mediated AR activation in CRPC.
• The LBCS-hnRNPK-AR axis presents a promising therapeutic target for treating CRPC.