The Impact of TRPM8 on Prostate Cancer Transcriptomic Dynamics

Area of Science:

• Oncology
• Molecular Biology
• Urology

Background:

• Prostate cancer (PC) progression is significantly influenced by androgen receptor (AR) signaling.
• The role of the Transient Receptor Potential Melastatin 8 (TRPM8) channel in PC pathogenesis is not fully understood.
• Investigating TRPM8's interaction with AR and its impact on oncogenic pathways is crucial for understanding PC aggressiveness.

Purpose of the Study:

• To investigate the expression patterns of TRPM8 in prostate cancer tissues.
• To elucidate the functional role of TRPM8 in AR signaling and oncogenic pathways.
• To determine if TRPM8 acts as a suppressor of PC progression and metastasis.

Main Methods:

• Analysis of TRPM8 and AR mRNA expression in PC tissues.
• RNA sequencing and pathway enrichment analysis (including GSEA) in TRPM8 knockout (KO) prostates.
• Evaluation of key metastatic genes (e.g., MMP2, FAP) and oncogenic pathways (e.g., angiogenesis, EMT).

Main Results:

• TRPM8 is upregulated in benign and early-stage PC but downregulated in metastatic samples.
• TRPM8 downregulation correlates with increased AR expression, suggesting enhanced AR-driven tumorigenesis.
• TRPM8 KO prostates show altered gene expression favoring metastasis, proliferation, and survival, with enriched androgen response, angiogenesis, and EMT pathways.

Conclusions:

• TRPM8 acts as a molecular brake on prostate cancer progression.
• Loss of TRPM8 contributes to aggressive disease phenotypes and enhances AR-driven tumorigenesis.
• TRPM8 represents a potential therapeutic target and biomarker for prostate cancer management.