Krt4-KO Mouse

Krt4, short for Keratin 4, is a gene that provides instructions for the production of keratin proteins. Keratins are key components in maintaining the structure and integrity of epithelial cells. Krt4 is involved in multiple biological processes related to epithelial cell function, and its dysregulation can impact normal tissue homeostasis [1,2,3,4,5,6].

In oral squamous cell carcinoma (OSCC), Krt4 is downregulated. Overexpression of hsa_circ_0096042, which binds to miR-1288-3p, can restrain OSCC cell proliferation by upregulating Krt4 as it is a target gene of miR-1288-3p [1]. Also, in OSCC, m6A methylation of exon-intron boundaries suppresses Krt4 pre-mRNA splicing by preventing the binding of DGCR8 [2]. In esophageal squamous cell carcinoma (ESCC), KRT4 is downregulated, and overexpressed RBM15 promotes cell proliferation and migration through the miR-3605-5p/KRT4 pathway, with miR-3605-5p targeting KRT4 [3].

In conclusion, Krt4 plays a crucial role in maintaining normal epithelial cell function. Its dysregulation, as seen in OSCC and ESCC, contributes to cancer progression. Understanding the molecular mechanisms related to Krt4 in these disease conditions through functional studies can potentially lead to the development of novel therapeutic strategies.

References:

1. Wang, Lu, Ma, Xin, Yu, Jie, Lou, Ying. 2022. Negative regulation of miR-1288-3p/KRT4 axis through a circular RNA in oral cancer. In Journal of biochemical and molecular toxicology, 36, e23118. doi:10.1002/jbt.23118. https://pubmed.ncbi.nlm.nih.gov/35707935/

2. Li, Xiaoxu, Fang, Juan, Tao, Xiaoan, Cheng, Bin, Wang, Yun. 2023. Splice site m6A methylation prevents binding of DGCR8 to suppress KRT4 pre-mRNA splicing in oral squamous cell carcinoma. In PeerJ, 11, e14824. doi:10.7717/peerj.14824. https://pubmed.ncbi.nlm.nih.gov/36811004/

3. Wang, Huan. 2024. The RNA m6A writer RBM15 contributes to the progression of esophageal squamous cell carcinoma by regulating miR-3605-5p/KRT4 pathway. In Heliyon, 10, e24459. doi:10.1016/j.heliyon.2024.e24459. https://pubmed.ncbi.nlm.nih.gov/38312624/

4. Liu, Dan, Zhang, Tianyu, Zhou, Hangfan, Li, Taiwen, Jiang, Lu. 2024. Malignant transformation of white sponge nevus: a case report of a novel keratin 4 mutation. In BMC oral health, 24, 588. doi:10.1186/s12903-024-04300-y. https://pubmed.ncbi.nlm.nih.gov/38773401/

5. Zhang, Jianming, Quan, Jingjing, Ren, Yongyuan, Yang, Jie, Zhang, Xu. 2018. Keratin 4 regulates the development of human white sponge nevus. In Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, 47, 598-605. doi:10.1111/jop.12728. https://pubmed.ncbi.nlm.nih.gov/29738605/

6. Rauf, Saqib, Ullah, Sami, Abid, Muhammad Adil, Ahmad, Sidra, Faisal, Sulaiman. 2024. A computational study of gene expression patterns in head and neck squamous cell carcinoma using TCGA data. In Future science OA, 10, 2380590. doi:10.1080/20565623.2024.2380590. https://pubmed.ncbi.nlm.nih.gov/39140365/