Serpine2, also known as Protease Nexin-1, is a serine proteinase inhibitor. Its target specificity can be influenced by extracellular matrix components. It has variable expression in many organs during development, adult stages, pathological situations or after injury. Genetically modified mice serve as useful in vivo models to study its functions [4].

In cancer research, Serpine2 knockdown has been shown to improve tumor radiosensitivity in lung cancer, as it reduces homologous recombination repair, suppresses cell migration and invasion, and inhibits the accumulation of p-ATM and RAD51 during DNA repair [1]. In liver cancer, SERPINE2 promotes metastasis by inhibiting c-Cbl-mediated EGFR ubiquitination and degradation, and its knockdown enhances the efficacy of sorafenib and lenvatinib [2]. In advanced renal cell carcinoma, SERPINE2 knockdown suppresses cell growth and invasion, while overexpression promotes metastasis, and it can activate the epithelial-mesenchymal transition pathway [3]. In esophageal squamous cell carcinoma, SERPINE2 knockdown inhibits tumor cell invasion and metastasis by inducing epithelial-mesenchymal transition through downregulating BMP4 [5]. In urothelial carcinoma, high SERPINE2 expression is associated with adverse pathologic features and poor prognosis [6]. In hepatoblastoma, SERPINE2 overexpression promotes cell migration, invasion, and suppresses apoptosis, and its upregulation is related to poor prognosis [10]. In oral squamous cell carcinoma, SERPINE2 promotes angiogenesis and lymphangiogenesis, and is an independent poor prognostic factor [9]. In human papillary thyroid carcinoma, SERPINE2 forms a positive feedback with EGF/EGFR to regulate cell proliferation, invasion and migration [8].

In conclusion, Serpine2 plays significant roles in multiple biological processes, especially in cancer-related functions such as tumor metastasis, radioresistance, and cell-cycle-related DNA repair. The use of gene knockout or knockdown models in various cancer types has provided crucial insights into Serpine2's functions, suggesting it could be a potential therapeutic target in these diseases. Additionally, in inner ear research, overexpression of Serpine2 promotes hair cell regeneration, indicating its role in tissue repair and regeneration [7].