CCDC137, a gene in the coiled-coil domain containing (CCDC) family, is involved in multiple biological processes and disease-related pathways. It has been implicated in pathways such as the β-catenin and AKT pathways, which are crucial in tumor development [1,3].

In hepatocellular carcinoma (HCC), elevated CCDC137 expression is closely correlated with poor prognosis. Mechanistically, CCDC137 binds to LZTS2, a negative regulator of β-catenin, and promotes its K48-linked poly-ubiquitination via recruiting E3 ubiquitin ligase β-TrCP in the nucleus, thus activating the AKT and β-catenin pathways [1]. In addition, CCDC137 binds with FOXM1, JTV1, LASP1 and FLOT2 mRNAs to increase their cytoplasmic localization, activating AKT signaling and promoting HCC [3].

In colorectal cancer, CDK12 orchestrates super-enhancer-associated CCDC137 transcription, enhancing cellular survival, proliferation, stemness and liver metastasis [2]. Pan-cancer analysis shows CCDC137 is over-expressed in various tumors, positively correlated with tumor-associated macrophages and cancer-associated fibroblasts, and with immunosuppressive genes, suggesting its role as an oncogene [4].

In lung adenocarcinoma, a proposed CPSF1-CCDC137 oncogenic axis was reported, with downregulated CCDC137 suppressing the malignant tumor phenotype and growth [5].

In conclusion, CCDC137 is significantly involved in cancer-related biological processes, especially in the development of HCC, colorectal cancer and lung adenocarcinoma. Its over-expression is often associated with poor prognosis and tumor-promoting effects, highlighting its potential as a therapeutic target in these cancer types.