Padi1, or peptidylarginine deiminase 1, catalyzes protein citrullination, a post-translational modification that impacts protein function [5]. It has been associated with regulating immune responses, with its expression linked to pathways in the tumor immune microenvironment [2]. Padi1 also plays a role in the regulation of chromatin structure and gene activity via histone citrullination, being essential for early embryo development [7].

In cancer research, Padi1 has shown oncogenic properties. In pancreatic ductal adenocarcinoma (PAAD), it promotes the epithelial-mesenchymal transition (EMT) by activating the ERK1/2-p38 signaling pathway. Knockdown of Padi1 in CFPAN-1 and HPAC cells suppressed cell migration and invasion, while overexpression in PANC-1 and Bxpc-3 cells had the opposite effect [1]. In colorectal cancer, Padi1 is highly expressed, and a risk-prognosis score based on its co-expressed genes can predict prognosis and immunotherapy efficacy [2]. In nasopharyngeal carcinoma, the lncRNA TINCR-mediated regulation of the Padi1-MAPK-MMP2/9 pathway promotes tumor progression and chemoresistance [3]. Oncolytic viruses expressing Padi1 exhibit anti-tumor activity against melanoma, increasing the percentage of activated CD8+ T cells in tumor-infiltrating lymphocytes [4]. Also, Padi1 and Padi3 regulate glycolysis and cancer cell proliferation by citrullinating pyruvate kinase M2 [6].

In conclusion, Padi1 is a crucial enzyme in various biological processes, especially in the context of embryonic development and cancer. Its role in promoting cancer cell metastasis and its association with the tumor immune microenvironment make it a potential target for cancer therapy. The gene knockout or knockdown studies in cancer cell lines have significantly contributed to understanding its function in cancer-related biological processes [1,2,3,4,6].