Pirin: a potential novel therapeutic target for castration-resistant prostate cancer regulated by miR-455-5p

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Androgen deprivation therapy is a common prostate cancer (PCa) treatment, but resistance leads to castration-resistant prostate cancer (CRPC).
• Novel biomarkers and therapeutic targets are crucial for effective PCa management.
• MicroRNA (miRNA) passenger strands represent an emerging area in cancer research.

Purpose of the Study:

• To investigate the role of the miR-455 duplex in PCa progression.
• To identify potential diagnostic markers and therapeutic targets for PCa, including CRPC.
• To elucidate the function of the miR-455-5p/pirin (PIR) axis in PCa aggressiveness.

Main Methods:

• RNA sequencing to analyze miRNA expression signatures in PCa.
• Bioinformatic analysis of The Cancer Genome Atlas patient cohort to correlate miRNA target gene expression with prognosis.
• Loss-of-function assays (siRNA, inhibitor) to assess the impact of PIR downregulation on cancer cell behavior.
• Analysis of PIR expression in hormone-sensitive prostate cancer (HSPC) and CRPC specimens.

Main Results:

• Both miR-455-5p and miR-455-3p demonstrated antitumor properties in PCa cells.
• Expression of eight miR-455-5p/-3p target genes, including PIR, was significantly associated with poor PCa patient prognosis.
• PIR expression was upregulated in both HSPC and CRPC tissues and directly regulated by miR-455-5p.
• Downregulation of PIR inhibited PCa cell migration and invasion, indicating its role in cancer aggressiveness.
• The miR-455-5p/PIR axis was identified as a contributor to PCa cell aggressiveness.

Conclusions:

• Pirin (PIR) is a promising diagnostic marker for both HSPC and CRPC.
• Targeting the miR-455-5p/PIR axis presents a potential future therapeutic strategy for CRPC.
• The discovery of antitumor miRNAs, including passenger strands, can advance the development of new diagnostic and therapeutic approaches for CRPC.