Ccdc154-KO Mouse

Ccdc154, Coiled-Coil Domain-Containing 154, is a gene with diverse functions. It is involved in cell cycle regulation as overexpression can induce G2/M arrest, and is related to osteopetrosis-a skeletal bone disorder [4]. It may also participate in pathways relevant to cancer development and neurodegenerative diseases based on its association with processes like cell proliferation, metastasis in cancer, and its role as a potential biomarker in Parkinson's disease [2,3,5].

In a mouse model, a spontaneous mutation of Ccdc154 led to congenital deafness in homozygous mutant mice. These mice showed abnormal bony remodeling of the otic capsule, characterized by increased vascularization and multiple cavitary lesions, while the structure of the organ of Corti, hair cells, and spiral ganglion neurons remained normal. This indicates that Ccdc154 mutation-induced bony remodeling disorders in the auditory ossicles and otic capsule are involved in hearing loss [1]. In liver cancer cells, knockdown of Ccdc154 inhibited proliferation, migration, invasion, and increased apoptosis, potentially through reducing Snail expression [2]. In colorectal cancer, high expression of Ccdc154 was associated with poor survival, and it interacted with MCM2 to promote the malignant phenotype [3].

In conclusion, Ccdc154 is crucial in cell cycle regulation, bone remodeling, and is involved in the development of certain cancers. Mouse models, especially those with Ccdc154 mutations, have revealed its role in syndromic hereditary deafness. Its study in cancer cell lines has provided insights into its function in cancer development, contributing to our understanding of these biological processes and associated disease mechanisms [1,2,3,4].

References:

1. Xu, Kai, Bai, Xue, Chen, Sen, Li, He, Sun, Yu. 2021. CCDC154 Mutant Caused Abnormal Remodeling of the Otic Capsule and Hearing Loss in Mice. In Frontiers in cell and developmental biology, 9, 637011. doi:10.3389/fcell.2021.637011. https://pubmed.ncbi.nlm.nih.gov/33614666/

2. Ma, Rulan, Nie, Hongmei, Mo, Caijing, Zhu, Kun, Li, Kang. 2025. CCDC154 knockdown inhibits growth of liver cancer via suppressing expression of Snail. In European journal of medical research, 30, 59. doi:10.1186/s40001-025-02290-3. https://pubmed.ncbi.nlm.nih.gov/39885494/

3. Hong, Wei-Feng, Zhu, De-Xiang, Chen, Yan-Jie, Liu, Tian-Shu, Liang, Li. 2023. Coiled-coil domain-containing 154 promotes colorectal cancer proliferation and metastasis via interacting with minichromosome maintenance complex component 2. In Cancer letters, 578, 216460. doi:10.1016/j.canlet.2023.216460. https://pubmed.ncbi.nlm.nih.gov/37863352/

4. Liao, Wanqin, Zhao, Rongsen, Lu, Liting, Deng, Yuezhen, Lu, Xincheng. 2012. Overexpression of a novel osteopetrosis-related gene CCDC154 suppresses cell proliferation by inducing G2/M arrest. In Cell cycle (Georgetown, Tex.), 11, 3270-9. doi:10.4161/cc.21642. https://pubmed.ncbi.nlm.nih.gov/22895184/

5. Dong, Wenwen, Qiu, Chang, Gong, Dawei, Zhang, Li, Zhang, Wenbin. 2019. Proteomics and bioinformatics approaches for the identification of plasma biomarkers to detect Parkinson's disease. In Experimental and therapeutic medicine, 18, 2833-2842. doi:10.3892/etm.2019.7888. https://pubmed.ncbi.nlm.nih.gov/31572530/