APOBEC3C Suppresses Prostate Cancer by Regulating Key Molecules Involved in Cellular Inflammation, Cell Cycle Arrest,...

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Prostate cancer (PCa) incidence is rising, with advanced, therapy-resistant stages posing significant clinical challenges.
• Identifying novel molecular drivers is crucial for understanding and treating advanced PCa.
• The need for new therapeutic targets in PCa necessitates research into its underlying molecular mechanisms.

Purpose of the Study:

• To identify and characterize novel molecular drivers in prostate cancer.
• To investigate the role of APOBEC3C (A3C) in PCa progression and its clinical significance.
• To elucidate the functional mechanisms by which A3C influences PCa cell behavior and the tumor microenvironment.

Main Methods:

• Transcriptomic data analysis (TCGA, GEO) using WGCNA, differential expression, and LASSO regression to identify candidate genes.
• Kaplan-Meier survival analysis to assess clinical relevance of candidate genes.
• In vitro gain- and loss-of-function assays (cell proliferation, migration, invasion) and molecular analyses (Western blot, IHC) to validate A3C function and mechanisms.

Main Results:

• APOBEC3C (A3C) was significantly downregulated in PCa, correlating with advanced stage, higher Gleason scores, and worse survival.
• High A3C expression was linked to an activated anti-tumor immune microenvironment (increased CD8+ T cells, decreased M2 macrophages, upregulated CD40).
• In vitro, A3C suppressed PCa cell proliferation, migration, and invasion, while A3C knockdown promoted these malignant phenotypes.

Conclusions:

• APOBEC3C (A3C) functions as a tumor suppressor in prostate cancer.
• A3C impedes PCa progression by modulating inflammation (STING1 pathway), cell cycle arrest (GAS1), and DNA damage response (GSTP1, GPX3).
• A3C represents a potential therapeutic target for managing advanced prostate cancer.