METTL3 facilitates prostate cancer progression via inducing HOXC6 m6A modification and stabilizing its expression...

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Prostate cancer (PCa) progression is linked to Homeobox C6 (HOXC6) and methyltransferase-like 3 (METTL3).
• The precise mechanism of HOXC6's oncogenic role in PCa via METTL3-mediated N6-methyladenosine (m6A) modification remains unclear.

Purpose of the Study:

• To investigate the role of HOXC6 and METTL3 in prostate cancer progression.
• To elucidate the mechanism of METTL3-mediated m6A modification in regulating HOXC6 expression and its impact on PCa.

Main Methods:

• Cell Counting Kit-8 (CCK-8), EdU, flow cytometry, transwell, scratch, and sphere formation assays for cellular analyses.
• Glycolysis assessment, RNA immunoprecipitation (Me-RIP), Co-immunoprecipitation, and in vivo tumor formation experiments.
• Analysis of m6A modification, protein interactions, and gene expression in PCa tissues and cells.

Main Results:

• HOXC6 and METTL3 were highly expressed in PCa tissues and cells.
• Silencing HOXC6 or METTL3 suppressed PCa cell proliferation, invasion, migration, stemness, and glycolysis.
• METTL3 stabilized HOXC6 expression via m6A modification, with IGF2BP2 acting as an m6A reader that recognized and bound to HOXC6 mRNA, maintaining its stability.

Conclusions:

• METTL3 promotes PCa progression by stabilizing HOXC6 expression through an m6A-IGF2BP2-dependent mechanism.
• HOXC6 interacts with the glycolytic enzyme PGK1, suggesting a role in regulating cellular metabolism.
• Targeting the METTL3-HOXC6-IGF2BP2 axis may offer therapeutic strategies for prostate cancer.