Cdkn2c, also known as p18INK4C, is a cell growth regulator that controls cell cycle progression by inhibiting cyclin-dependent kinases. It is involved in multiple pathways related to metabolism, cancer development, and cell differentiation, and thus is of great biological importance. Genetic models, such as gene knockout mouse models, can be used to study its function [1,2,3,4,5,6,7,8].

In adipose tissue, Cdkn2c mRNA expression is reduced in type II diabetes and obese subjects. Knockdown of Cdkn2c in human preadipocytes led to lower expression of differentiation markers and transiently reduced lipid accumulation during adipocyte differentiation, suggesting its role in adipose lipid storage [1]. In sporadic medullary thyroid carcinoma, loss of Cdkn2c is associated with worse M stage, overall AJCC stage, and decreased overall survival, especially when combined with RETM918T mutation [2]. In leiomyosarcoma, CDKN2C-null tumors represent a genomically distinct class with unique genetic alterations, rare TP53, RB1, and ATRX mutations, and frequent CIC genomic alterations and 1p/19q-codeletion [3]. In gastric cancer, c-Myc and PRMT5 interact to transcriptionally repress Cdkn2c expression to promote cell growth [4]. In lung adenocarcinoma, CBX8 promotes tumor growth and metastasis by transcriptionally repressing Cdkn2c [5]. In multiple myeloma, deletions of Cdkn2c are associated with worse overall survival, and cases with homozygous deletions are the most proliferative [8].

In conclusion, Cdkn2c plays essential roles in cell cycle regulation, adipocyte differentiation, lipid storage, and is implicated in various diseases like diabetes, multiple types of cancer. Gene knockout or knockdown models have been crucial in revealing these functions, providing insights into disease mechanisms and potential therapeutic targets in these disease areas.

References:

1. Pereira, Maria J, Vranic, Milica, Kamble, Prasad G, Hetty, Susanne, Eriksson, Jan W. 2021. CDKN2C expression in adipose tissue is reduced in type II diabetes and central obesity: impact on adipocyte differentiation and lipid storage? In Translational research : the journal of laboratory and clinical medicine, 242, 105-121. doi:10.1016/j.trsl.2021.12.003. https://pubmed.ncbi.nlm.nih.gov/34896253/

2. Grubbs, Elizabeth G, Williams, Michelle D, Scheet, Paul, Cabanillas, Maria E, Cote, Gilbert J. 2016. Role of CDKN2C Copy Number in Sporadic Medullary Thyroid Carcinoma. In Thyroid : official journal of the American Thyroid Association, 26, 1553-1562. doi:. https://pubmed.ncbi.nlm.nih.gov/27610696/

3. Williams, Erik A, Sharaf, Radwa, Decker, Brennan, Ramkissoon, Shakti H, Elvin, Julia A. 2020. CDKN2C-Null Leiomyosarcoma: A Novel, Genomically Distinct Class of TP53/RB1-Wild-Type Tumor With Frequent CIC Genomic Alterations and 1p/19q-Codeletion. In JCO precision oncology, 4, . doi:10.1200/PO.20.00040. https://pubmed.ncbi.nlm.nih.gov/33015533/

4. Liu, Ming, Yao, Bing, Gui, Tao, Ju, Junyi, Zhao, Quan. 2020. PRMT5-dependent transcriptional repression of c-Myc target genes promotes gastric cancer progression. In Theranostics, 10, 4437-4452. doi:10.7150/thno.42047. https://pubmed.ncbi.nlm.nih.gov/32292506/

5. Chen, Hao, Su, Yijie, Yang, Lihong, Liu, Min, Xuan, Chenghao. 2023. CBX8 promotes lung adenocarcinoma growth and metastasis through transcriptional repression of CDKN2C and SCEL. In Journal of cellular physiology, 238, 2710-2723. doi:10.1002/jcp.31124. https://pubmed.ncbi.nlm.nih.gov/37733753/

6. El Naofal, Maha, Kim, Adriel, Yon, Hui Yi, Cote, Gilbert J, Hu, Peter. . Role of CDKN2C Fluorescence In Situ Hybridization in the Management of Medullary Thyroid Carcinoma. In Annals of clinical and laboratory science, 47, 523-528. doi:. https://pubmed.ncbi.nlm.nih.gov/29066476/

7. Eller, Carla, Heydmann, Laura, Colpitts, Che C, Verrier, Eloi R, Baumert, Thomas F. 2020. A genome-wide gain-of-function screen identifies CDKN2C as a HBV host factor. In Nature communications, 11, 2707. doi:10.1038/s41467-020-16517-w. https://pubmed.ncbi.nlm.nih.gov/32483149/

8. Leone, Paola E, Walker, Brian A, Jenner, Matthew W, Davies, Faith E, Morgan, Gareth J. . Deletions of CDKN2C in multiple myeloma: biological and clinical implications. In Clinical cancer research : an official journal of the American Association for Cancer Research, 14, 6033-41. doi:10.1158/1078-0432.CCR-08-0347. https://pubmed.ncbi.nlm.nih.gov/18829482/