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Updated: Jan 17, 2026
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
CCDC137 knockdown suppresses bladder cancer progression by downregulating SCD
Haiyu Zhang1,2,3,4,5, Weisheng Huang1,2,3,4,5, Zhimao Cai6,7
1Shantou University Medical College, Shantou, 515000, China.
Background:
The Coiled-coil domain-containing (CCDC) family, due to its unique protein structural domain and broad involvement in diverse biological processes, has emerged as a focus in oncology research. Nevertheless, its clinical significance and function in bladder cancer (BLCA) remain poorly defined.
Methods:
Machine learning algorithms were employed to identify pivotal CCDC genes in the cancer genome atlas (TCGA), and a prognostic model was subsequently constructed. Multi-omics data encompassing pan-cancer cohorts, single-cell sequencing, and spatial transcriptomics were integrated to characterize the expression patterns and prognostic significance of Coiled-coil domain-containing 137 (CCDC137), a previously uncharacterized CCDC family member in BLCA. Tissue microarray confirmed CCDC137 abnormal expression in bladder carcinoma specimens. The effect of CCDC137 knockdown on BLCA progression was evaluated through CCK8 assay, clonogenic formation, wound healing, Transwell, and subcutaneous xenograft models. RNA sequencing, quantitative RT-PCR, and western blot were utilized to delineate its regulatory network.
Results:
A prognostic model incorporating 10 CCDC genes was successfully established in the TCGA-BLCA cohort. Then, we found that CCDC137 exhibited pan-cancer overexpression and usually correlation with poor clinical outcomes. Immunohistochemistry further substantiated its dysregulation in bladder carcinoma. Integrated multi-omics analyses suggested associations between CCDC137 expression and a tumor immunosuppressive microenvironment. CCDC137 knockdown significantly suppressed bladder cancer cell proliferation and migratory capacity in vitro. Correspondingly, subcutaneous xenograft tumor growth was inhibited in vivo. Moreover, decreased expression of stearoyl-CoA desaturase (SCD), a key lipid metabolic enzyme, accompanied CCDC137 depletion. These findings collectively suggest a cancer-promoting role for CCDC137 in bladder carcinoma.
Conclusions:
This systematic investigation combining multi-omics bioinformatics analyses and experimental validation demonstrates the role of CCDC137 in bladder carcinoma progression, providing novel mechanistic insights into the pathogenesis of BLCA and offering a theoretical foundation for therapeutic targeting of CCDC137 in urothelial malignancies.
Insights
Coiled-coil domain-containing 137 (CCDC137) promotes bladder cancer (BLCA) progression by influencing the tumor microenvironment and lipid metabolism. Targeting CCDC137 offers a potential therapeutic strategy for urothelial malignancies.
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.
