PLCE1, or phospholipase C epsilon 1, is a member of the phospholipase C (PLC) family, controlling phosphoinositide levels in cells. It is involved in multiple biological processes such as cell growth, differentiation, and is associated with pathways like PKCα-E2F1-MCM7 and phosphoinositide-mediated cell death regulation. It has been identified as a susceptibility gene in several diseases, highlighting its biological importance [1,2].

In esophageal squamous cell carcinoma (ESCC), PLCE1 promotes tumor progression. It activates PKCα-mediated phosphorylation of E2F1, upregulating MCM7 and miR-106b-5p expression, and potentiates MCM7 phosphorylation by RIOK2 [1]. In doxorubicin-induced cardiotoxicity, PLCE1 enhances mitochondrial dysfunction to promote GSDME-mediated pyroptosis, while its deletion ameliorates mitochondrial dysfunction and reduces pyroptotic cell death [2]. In podocytes, PLCE1 knockout leads to decreased Rho GTPase activity, reduced cell migration, and affects cell proliferation and differentiation [3].

In summary, PLCE1 plays crucial roles in multiple biological processes and disease conditions. Studies on PLCE1 using gene knockout models have provided insights into its functions in cancer, cardiotoxicity, and nephrotic syndrome-related processes, enhancing our understanding of disease mechanisms and potentially paving the way for new therapeutic strategies.

References:

1. Shi, Qi, Xu, Guixuan, Jiang, Yuliang, Cui, Xiaobin, Li, Feng. . Phospholipase PLCE1 Promotes Transcription and Phosphorylation of MCM7 to Drive Tumor Progression in Esophageal Cancer. In Cancer research, 84, 560-576. doi:10.1158/0008-5472.CAN-23-1633. https://pubmed.ncbi.nlm.nih.gov/38117512/

2. Tuersuntuoheti, Maierhaba, Peng, Fei, Li, Juexing, Gao, Hailan, Gong, Hui. 2024. PLCE1 enhances mitochondrial dysfunction to promote GSDME-mediated pyroptosis in doxorubicin-induced cardiotoxicity. In Biochemical pharmacology, 223, 116142. doi:10.1016/j.bcp.2024.116142. https://pubmed.ncbi.nlm.nih.gov/38499110/

3. Yu, Seyoung, Choi, Won-Il, Choi, Yo Jun, Hildebrandt, Friedhelm, Gee, Heon Yung. 2020. PLCE1 regulates the migration, proliferation, and differentiation of podocytes. In Experimental & molecular medicine, 52, 594-603. doi:10.1038/s12276-020-0410-4. https://pubmed.ncbi.nlm.nih.gov/32238860/