Cldn8, also known as Claudin 8, is an integral membrane protein that forms tight junctions in cell membranes. Tight junctions restrict paracellular fluxes to mineral ions and aqueous molecules, and Cldn8 may be involved in controlling paracellular fluxes of amino acids [6]. It is also associated with various signaling pathways, such as the MAPK/ERK pathway, and plays a role in cell proliferation, migration, and invasion [2].

In kidney renal clear cell carcinoma (KIRC), knocking out Cldn8 stimulated cell proliferation, suggesting it may act as a tumor suppressor [1]. In colorectal cancer, knockdown of Cldn8 suppressed cell proliferation, migration, and invasion, while overexpression promoted tumor progression, with the MAPK/ERK signaling pathway being involved [2]. In prostate cancer, Cldn8, an androgen-regulated gene, promoted cell proliferation and migration [3]. In psoriasis, hsa-miR-31-3p targets Cldn8, compromising skin barrier integrity [4]. In Crohn's disease, SOX9 negatively regulated Cldn8 expression, and miR-145-5p affected this pathway, impairing intestinal mucosal barrier homeostasis [5].

In conclusion, Cldn8 plays essential roles in maintaining barrier functions in various tissues and is involved in the development and progression of multiple diseases including cancers, psoriasis, and Crohn's disease. Gene knockout studies in these contexts have significantly contributed to understanding its function, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Ji, Han Chu, Li, Jian Di, Zhang, Guan Lan, Chen, Gang, Qin, Bin. 2024. Significance and Possible Biological Mechanism for CLDN8 Downregulation in Kidney Renal Clear Cell Carcinoma Tissues. In World journal of oncology, 15, 662-674. doi:10.14740/wjon1869. https://pubmed.ncbi.nlm.nih.gov/38993257/

2. Cheng, Bo, Rong, Aimei, Zhou, Quanbo, Li, Wenlu. 2019. CLDN8 promotes colorectal cancer cell proliferation, migration, and invasion by activating MAPK/ERK signaling. In Cancer management and research, 11, 3741-3751. doi:10.2147/CMAR.S189558. https://pubmed.ncbi.nlm.nih.gov/31118793/

3. Ashikari, Daisaku, Takayama, Ken-Ichi, Obinata, Daisuke, Takahashi, Satoru, Inoue, Satoshi. 2017. CLDN8, an androgen-regulated gene, promotes prostate cancer cell proliferation and migration. In Cancer science, 108, 1386-1393. doi:10.1111/cas.13269. https://pubmed.ncbi.nlm.nih.gov/28474805/

4. Tu, Yunhua, Wang, Li, An, Lijun, He, Li. 2025. Hsa-miR-31-3p targets CLDN8 to compromise skin barrier integrity in psoriasis. In Biochemistry and biophysics reports, 42, 101976. doi:10.1016/j.bbrep.2025.101976. https://pubmed.ncbi.nlm.nih.gov/40160514/

5. Zhuang, Xiaojun, Chen, Baili, Huang, Shanshan, Zeng, Zhirong, Zhang, Shenghong. 2022. Hypermethylation of miR-145 promoter-mediated SOX9-CLDN8 pathway regulates intestinal mucosal barrier in Crohn's disease. In EBioMedicine, 76, 103846. doi:10.1016/j.ebiom.2022.103846. https://pubmed.ncbi.nlm.nih.gov/35124427/

6. Okamoto, Ema, Matsuda, Shunsuke, Yoshino, Yuta, Matsunaga, Toshiyuki, Ikari, Akira. 2023. Regulation of Paracellular Fluxes of Amino Acids by Claudin-8 in Normal Mouse Intestinal MCE301 Cells. In Nutrients, 15, . doi:10.3390/nu15061346. https://pubmed.ncbi.nlm.nih.gov/36986076/