Cdkn1a-KO Mouse

Cdkn1a, also known as Cyclin-dependent kinase inhibitor 1A and with aliases such as Cip1/Waf1/p21, is a well-established protein. It is primarily recognized for its key role in the cell cycle, where it induces cell cycle arrest by inhibiting cyclin-dependent kinases (CDKs). Besides, it is involved in apoptosis, DNA damage response (DDR), and the regulation of stem cell fate [1].

In cisplatin-induced acute kidney injury (AKI), CDKN1A was identified as a key gene related to ferroptosis and the P53 pathway. Knockdown of CDKN1A in human renal tubular epithelial cells mitigated cisplatin-induced cell injury by reducing oxidative stress and ferroptosis, suggesting its potential as a biomarker for early diagnosis and a therapeutic target in AKI [2]. In esophageal cancer, CDKN1A polymorphisms were found to be associated with EC risk in relation to age. For example, certain genotypes and alleles were significantly associated with EC risk in different age groups [3]. In an Iranian population, the AC genotype of CDKN1A rs1801270 polymorphism may have a protective role in the development of colorectal cancer [4].

In conclusion, Cdkn1a is crucial for cell cycle regulation and is involved in multiple biological processes. Studies on Cdkn1a, especially through functional studies in relevant disease models like AKI and cancer, have revealed its significance in disease pathogenesis. These findings contribute to understanding the mechanisms of disease occurrence and may provide new directions for diagnosis and treatment.

References:

1. Manousakis, Evangelos, Miralles, Clàudia Martinez, Esquerda, Maria Guimerà, Wright, Roni H G. 2023. CDKN1A/p21 in Breast Cancer: Part of the Problem, or Part of the Solution? In International journal of molecular sciences, 24, . doi:10.3390/ijms242417488. https://pubmed.ncbi.nlm.nih.gov/38139316/

2. Gao, Qian, Chen, Jun-Ming, Li, Chen-Sui-Zi, Luo, Lian-Xiang, Li, Zhi-Ling. 2024. CDKN1A promotes Cis-induced AKI by inducing cytoplasmic ROS production and ferroptosis. In Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 193, 115003. doi:10.1016/j.fct.2024.115003. https://pubmed.ncbi.nlm.nih.gov/39353481/

3. Kaya, Zehra, Karan, Burak Mugdat, Almalı, Necat. 2021. CDKN1A (p21 gene) polymorphisms correlates with age in esophageal cancer. In Molecular biology reports, 49, 249-258. doi:10.1007/s11033-021-06865-1. https://pubmed.ncbi.nlm.nih.gov/34743275/

4. Zali, Neda, Savabkar, Sanaz, Tajali, Raziye, Hashemi, Mehrdad, Asadzadeh Aghdaei, Hamid. 2023. Association between CDKN1A gene rs1801270 polymorphisms and susceptibility to colorectal cancser in an Iranian population. In Nucleosides, nucleotides & nucleic acids, 42, 563-570. doi:10.1080/15257770.2023.2169934. https://pubmed.ncbi.nlm.nih.gov/36691945/