CCDC137 knockdown suppresses bladder cancer progression by downregulating SCD.

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• The Coiled-coil domain-containing (CCDC) protein family plays diverse biological roles, with emerging significance in cancer research.
• The specific function and clinical relevance of CCDC genes, particularly CCDC137, in bladder cancer (BLCA) are not well understood.

Purpose of the Study:

• To investigate the role of CCDC137 in the progression of bladder cancer (BLCA).
• To explore the potential of CCDC137 as a therapeutic target in urothelial malignancies.

Main Methods:

• Utilized machine learning on TCGA data to build a prognostic model for CCDC genes in BLCA.
• Integrated multi-omics data (pan-cancer, single-cell, spatial transcriptomics) to analyze CCDC137 expression and function.
• Performed in vitro and in vivo experiments (cell assays, xenografts) to assess the impact of CCDC137 knockdown.
• Employed RNA sequencing and Western blot to elucidate CCDC137's regulatory network.

Main Results:

• Established a prognostic model for 10 CCDC genes in the TCGA-BLCA cohort.
• CCDC137 was found to be overexpressed across multiple cancers, correlating with poor outcomes and dysregulation in bladder carcinoma.
• CCDC137 knockdown suppressed BLCA cell proliferation, migration, and tumor growth in vivo, linked to altered lipid metabolism (SCD).
• CCDC137 expression is associated with a tumor-suppressive microenvironment.

Conclusions:

• CCDC137 plays a significant cancer-promoting role in bladder carcinoma.
• This study provides mechanistic insights into BLCA pathogenesis and identifies CCDC137 as a potential therapeutic target for urothelial cancers.