Anxa8, a member of the annexins family, encodes an anticoagulant protein involved in the blood coagulation cascade and acts as an indirect inhibitor of the thromboplastin-specific complex [3]. It has been associated with multiple cellular processes including proliferation, metastasis, and inflammation, and is involved in signaling pathways such as EGFR-Akt-mTOR, Wnt/β-catenin, and the regulation of cell cycle-related proteins [2,4].

In various diseases, Anxa8 shows distinct roles. In gastric carcinoma, its over-expression is strongly correlated with TNM stages, differentiation grades, and is an independent prognostic factor for overall survival and disease-free survival, acting as an oncogene [1]. In non-small lung cancer cells A549, over-expression of Anxa8 promotes proliferation and migration via the EGFR-Akt-mTOR signaling pathway, while knockdown has the opposite effect [2]. In porcine endometrial cells, Anxa8 promotes proliferation through the Akt signaling pathway [3]. In ovarian cancer, interference with Anxa8 inhibits malignant progression by suppressing the activation of the Wnt/β-catenin signaling pathway via UCHL5 [4]. In atherosclerosis-prone mice, germline deletion of Anxa8 decreases atherosclerotic burden, plaque size, and macrophage accumulation, and endothelial-specific silencing of Anxa8 also reduces atherosclerosis progression, indicating that Anxa8 promotes atherosclerosis progression by modulating endothelial-leukocyte interactions [5]. In renal cell carcinoma, Anxa8 expression is increased and associated with poor prognosis, and knockdown of Anxa8 mainly influences the cell cycle and DNA replication [6]. In cholangiocarcinoma, ANXA8 inhibits cell migratory and metastatic characteristics, and its down-regulation by EGF-FOXO4 signaling is involved in tumor metastasis [7]. In cervical squamous cell carcinoma, the TFAP2A/Anxa8 axis regulates ferroptosis by mediating GSH synthesis [8].

In conclusion, Anxa8 is involved in multiple biological processes and disease conditions. Gene knockout or knockdown studies in various models have revealed its role in processes like cell proliferation, metastasis, and in diseases such as cancer and atherosclerosis. These studies provide insights into potential therapeutic strategies targeting Anxa8 for treating related diseases.