Padi1-KO Mouse

Padi1, or peptidylarginine deiminase 1, catalyzes protein citrullination, converting protein-bound arginine residues into citrulline residues in a calcium-dependent manner [7,8]. This post-translational modification is involved in various biological processes such as immune response regulation, and it has been associated with pathways like ERK1/2-p38 and MAPK-MMP2/9 [1,3]. Padi1 is important in normal physiological processes like early embryo development [6] and keratinocyte differentiation [7,9].

In pancreatic ductal adenocarcinoma (PAAD), knockdown of Padi1 in cell lines suppressed cell migration and invasion, suggesting it may function as an oncogene regulating metastasis in vitro, likely through the ERK1/2-p38 signaling pathway [1]. In colorectal cancer (CRC), Padi1 was highly expressed, and a set of its co-expressed genes could predict CRC prognosis and immunotherapy efficacy. The high-risk group of these co-expressed genes was enriched in pathways promoting immune escape [2]. In nasopharyngeal carcinoma, lncRNA TINCR regulated the Padi1-MAPK-MMP2/9 pathway, and Padi1 was involved in tumor progression and chemoresistance [3]. Oncolytic adenoviruses expressing Padi1 showed anti-tumor activity against melanoma in mouse models, increasing activated CD8+ T cells [4]. Padi1 and Padi3 citrullinated pyruvate kinase M2, regulating glycolysis and cancer cell proliferation [5].

In conclusion, Padi1 is crucial in multiple biological processes and diseases. Its role in tumor-related processes such as metastasis, immune microenvironment modulation, and glycolysis regulation, as revealed through in vitro and in vivo studies, offers potential therapeutic targets for cancers like PAAD, CRC, nasopharyngeal carcinoma, and melanoma. Additionally, its function in early embryo development highlights its significance in normal physiological development [1-7].

References:

1. Ji, Tengfei, Ma, Keqiang, Chen, Liang, Cao, Tiansheng. . PADI1 contributes to EMT in PAAD by activating the ERK1/2-p38 signaling pathway. In Journal of gastrointestinal oncology, 12, 1180-1190. doi:10.21037/jgo-21-283. https://pubmed.ncbi.nlm.nih.gov/34295566/

2. Zhang, Yi-Ran, Zhang, Lei, Li, Feng, Gong, Chao, Pan, Yun-Long. 2022. PADI1 and Its Co-Expressed Gene Signature Unveil Colorectal Cancer Prognosis and Immunotherapy Efficacy. In Journal of oncology, 2022, 8394816. doi:10.1155/2022/8394816. https://pubmed.ncbi.nlm.nih.gov/36471887/

3. Zheng, Zi-Qi, Li, Zhi-Xuan, Guan, Jia-Li, Liu, Na, Sun, Ying. 2020. Long Noncoding RNA TINCR-Mediated Regulation of Acetyl-CoA Metabolism Promotes Nasopharyngeal Carcinoma Progression and Chemoresistance. In Cancer research, 80, 5174-5188. doi:10.1158/0008-5472.CAN-19-3626. https://pubmed.ncbi.nlm.nih.gov/33067266/

4. Kuryk, Lukasz, Møller, Anne-Sophie W. 2023. Next generation oncolytic viruses expressing PADI1 and TIMP2 exhibit anti-tumor activity against melanoma in nude and humanized mouse models. In Molecular therapy oncolytics, 28, 158-170. doi:10.1016/j.omto.2023.01.002. https://pubmed.ncbi.nlm.nih.gov/36816748/

5. Coassolo, Sébastien, Davidson, Guillaume, Negroni, Luc, Romier, Christophe, Davidson, Irwin. 2021. Citrullination of pyruvate kinase M2 by PADI1 and PADI3 regulates glycolysis and cancer cell proliferation. In Nature communications, 12, 1718. doi:10.1038/s41467-021-21960-4. https://pubmed.ncbi.nlm.nih.gov/33741961/

6. Zhang, Xiaoqian, Liu, Xiaoqiu, Zhang, Mei, Coonrod, Scott A, Zhang, Xuesen. 2016. Peptidylarginine deiminase 1-catalyzed histone citrullination is essential for early embryo development. In Scientific reports, 6, 38727. doi:10.1038/srep38727. https://pubmed.ncbi.nlm.nih.gov/27929094/

7. Dong, Sijun, Ying, Shibo, Kojima, Toshio, Simon, Michel, Takahara, Hidenari. 2007. Crucial roles of MZF1 and Sp1 in the transcriptional regulation of the peptidylarginine deiminase type I gene (PADI1) in human keratinocytes. In The Journal of investigative dermatology, 128, 549-57. doi:. https://pubmed.ncbi.nlm.nih.gov/17851584/

8. Ying, Shibo, Dong, Sijun, Kawada, Akira, Simon, Michel, Takahara, Hidenari. 2008. Transcriptional regulation of peptidylarginine deiminase expression in human keratinocytes. In Journal of dermatological science, 53, 2-9. doi:10.1016/j.jdermsci.2008.09.009. https://pubmed.ncbi.nlm.nih.gov/19004619/

9. Hu, Lizhi, Bikle, Daniel D, Oda, Yuko. 2013. Reciprocal role of vitamin D receptor on β-catenin regulated keratinocyte proliferation and differentiation. In The Journal of steroid biochemistry and molecular biology, 144 Pt A, 237-41. doi:10.1016/j.jsbmb.2013.11.002. https://pubmed.ncbi.nlm.nih.gov/24239508/