Serpine1-KO Mouse

Serpine1, also known as Plasminogen Activator Inhibitor (PAI-1), is a key member of the serine proteinase inhibitor E superfamily and plays a crucial role in the fibrinolytic system [3]. It is involved in various biological processes and is associated with multiple diseases. The plasminogen/plasminase system, in which Serpine1 is a key modulator, is related to many physiological and pathological events [5]. Genetic models, such as studying its single nucleotide polymorphisms, can provide insights into its roles in diseases [2,4].

In colorectal cancer, therapy-induced senescent tumor cells release extracellular vesicles enriched in Serpine1, which promote cancer progression by binding to p65, facilitating its nuclear translocation, and activating the NF-κB signaling pathway [1]. In gastric cancer, Serpine1 is highly expressed, related to poor prognosis, and may regulate cuproptosis and the immune microenvironment, potentially serving as a prognostic biomarker and therapeutic target [7]. In head and neck cancer, overexpression of Serpine1 enhances tumor cell migration, invasion, and metastasis, conferring a poor prognosis, and it may be a potential drug target [6]. In colon cancer, Serpine1 is highly expressed, associated with different clinical features, and is a prognostic risk factor [8].

In conclusion, Serpine1 is essential in the fibrinolytic system and is involved in multiple disease-related processes. Model-based research, especially in the context of cancer, has revealed its role in promoting tumor progression, metastasis, and influencing prognosis in various cancers such as colorectal, gastric, head and neck, and colon cancer. This understanding of Serpine1's functions provides potential directions for therapeutic strategies in these disease areas.

References:

1. Zhang, Dan, Zhang, Jian-Wei, Xu, Hui, Peng, Jin, Zhou, Fu-Xiang. 2024. Therapy-induced senescent tumor cell-derived extracellular vesicles promote colorectal cancer progression through SERPINE1-mediated NF-κB p65 nuclear translocation. In Molecular cancer, 23, 70. doi:10.1186/s12943-024-01985-1. https://pubmed.ncbi.nlm.nih.gov/38576002/

2. Bahrami, Reza, Dastgheib, Seyed Alireza, Mirjalili, Hamid, Noorishadkam, Mahmood, Neamatzadeh, Hossein. 2021. Association of SERPINE1 rs1799889 polymorphism with arterial ischemic stroke in children: a systematic review and meta-analysis. In Nucleosides, nucleotides & nucleic acids, 40, 1018-1035. doi:10.1080/15257770.2021.1966798. https://pubmed.ncbi.nlm.nih.gov/34429017/

3. Chen, Teng-Yu, Zhou, Min, Lin, Man-Qing, Li, Dan, Ruan, Yan. 2021. Research Progress on the SERPINE1 Protein and Chronic Inflammatory Diseases of the Upper Respiratory Tract: A Literature Review. In International archives of allergy and immunology, 182, 1097-1102. doi:10.1159/000516195. https://pubmed.ncbi.nlm.nih.gov/33946071/

4. Chen, JingYi, Zhai, ChuanNan, Wang, ZhiQian, Wang, Yan, Cong, HongLiang. 2021. The susceptibility of SERPINE1 rs1799889 SNP in diabetic vascular complications: a meta-analysis of fifty-one case-control studies. In BMC endocrine disorders, 21, 195. doi:10.1186/s12902-021-00837-z. https://pubmed.ncbi.nlm.nih.gov/34592988/

5. Ju, Yuming, Wang, Zeshen, Wang, Qiancheng, Zhu, Guanyu, Wang, Kuan. . Pan-cancer analysis of SERPINE1 with a concentration on immune therapeutic and prognostic in gastric cancer. In Journal of cellular and molecular medicine, 28, e18579. doi:10.1111/jcmm.18579. https://pubmed.ncbi.nlm.nih.gov/39086142/

6. Pavón, Miguel Angel, Arroyo-Solera, Irene, Céspedes, Maria Virtudes, León, Xavier, Mangues, Ramón. . uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy. In Oncotarget, 7, 57351-57366. doi:10.18632/oncotarget.10344. https://pubmed.ncbi.nlm.nih.gov/27385000/

7. Feng, Leiran, Li, Guixin, Li, Dongbin, Duan, Guoqiang, Liu, Jin. 2023. Cuproptosis-related gene SERPINE1 is a prognostic biomarker and correlated with immune infiltrates in gastric cancer. In Journal of cancer research and clinical oncology, 149, 10851-10865. doi:10.1007/s00432-023-04900-1. https://pubmed.ncbi.nlm.nih.gov/37318594/

8. Wang, Yigang, Wang, Jinyan, Gao, Jianchao, Ding, Mei, Li, Hua. 2023. The expression of SERPINE1 in colon cancer and its regulatory network and prognostic value. In BMC gastroenterology, 23, 33. doi:10.1186/s12876-022-02625-y. https://pubmed.ncbi.nlm.nih.gov/36755247/