ANXA3,也称为Annexin A3或Lipocortin III,是一种钙依赖性磷脂结合蛋白。ANXA3属于Annexin家族,这些蛋白质在细胞信号传导、膜转运和炎症反应中发挥着重要作用。ANXA3的表达和功能异常与多种疾病的发生和发展密切相关,包括癌症、中风、肾病、糖尿病和自身免疫性疾病等。
ANXA3在肿瘤的发生和发展中起着重要作用。研究表明,ANXA3在多种癌症组织中表达上调,包括卵巢癌、乳腺癌和宫颈癌。ANXA3的表达水平与肿瘤的恶性程度、侵袭性和转移性密切相关。例如,在卵巢癌中,高表达ANXA3与淋巴结浸润和总生存期改善显著相关[1]。在乳腺癌中,ANXA3的表达水平与肿瘤的发生、发展和转移密切相关,并且与三阴性乳腺癌患者的预后不良相关[4]。在宫颈癌中,ANXA3的表达水平与肿瘤的恶性程度和化疗耐药性相关[5]。
ANXA3在中风的发生和发展中也发挥着重要作用。研究表明,ANXA3在缺血性中风中表达上调,并且与细胞焦亡的发生有关。ANXA3可能通过NLRC4/AIM2轴抑制细胞焦亡,从而减轻缺血性中风引起的组织损伤[2]。
ANXA3还与肾脏疾病的发生和发展相关。研究发现,ANXA3在IgA肾病的全基因组关联研究中被定义为一种新的风险基因,其表达水平与疾病的易感性和肾脏功能恶化相关[3]。
ANXA3与糖尿病的发生和发展也有关。研究表明,ANXA3在2型糖尿病骨折不愈合的患者中表达上调,并且与中性粒细胞在骨折愈合过程中的作用相关[6]。
ANXA3还与自身免疫性疾病的发生和发展相关。研究发现,ANXA3在抗磷脂综合征中表达上调,并且与血栓形成的风险增加相关[9]。
ANXA3的表达和功能异常还与其他疾病的发生和发展相关,例如血管异常、骨代谢异常和脊柱炎等。研究表明,EB病毒感染通过上调ANXA3-HIF-1α-VEGF通路导致上皮恶性肿瘤中的血管异常,并促进肿瘤的生长[7]。ANXA3的过表达还与骨折不愈合和脊柱炎的发生和发展相关[6][8]。
综上所述,ANXA3是一种重要的钙依赖性磷脂结合蛋白,在多种疾病的发生和发展中发挥着重要作用。ANXA3的表达和功能异常与肿瘤的发生、发展、转移和预后相关,还与中风、肾病、糖尿病和自身免疫性疾病的发生和发展相关。ANXA3可能成为新的治疗靶点和诊断标志物,为疾病的治疗和预防提供新的思路和策略[1][2][3][4][5][6][7][8][9]。
参考文献:
1. Li, De-Qiang, Lin, Mao, Abdelrahman, Zeinab. . High expression of the ANXA3 gene promotes immune infiltration and improves tumor prognosis in ovarian serous carcinoma using bioinformatics analyses. In Annals of translational medicine, 10, 1055. doi:10.21037/atm-22-3726. https://pubmed.ncbi.nlm.nih.gov/36330402/
2. Liu, Linquan, Cai, Yahong, Deng, Changqing. 2023. Identification of ANXA3 as a biomarker associated with pyroptosis in ischemic stroke. In European journal of medical research, 28, 596. doi:10.1186/s40001-023-01564-y. https://pubmed.ncbi.nlm.nih.gov/38102696/
3. Kiryluk, Krzysztof, Sanchez-Rodriguez, Elena, Zhou, Xu-Jie, Zhang, Hong, Gharavi, Ali G. 2023. Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy. In Nature genetics, 55, 1091-1105. doi:10.1038/s41588-023-01422-x. https://pubmed.ncbi.nlm.nih.gov/37337107/
4. Zhou, Tao, Liu, Svetlana, Yang, Li, Ju, Yingchao, Li, Chunxiao. . The expression of ANXA3 and its relationship with the occurrence and development of breast cancer. In Journal of B.U.ON. : official journal of the Balkan Union of Oncology, 23, 713-719. doi:. https://pubmed.ncbi.nlm.nih.gov/30003741/
5. Huang, Jiazhen, Wei, Wei, Kang, Fuli, Lu, Xiaohang, Wang, Ning. 2023. ANXA3, associated with YAP1 regulation, participates in the proliferation and chemoresistance of cervical cancer cells. In Genes & genomics, 45, 1575-1586. doi:10.1007/s13258-023-01461-y. https://pubmed.ncbi.nlm.nih.gov/37843781/
6. Liu, Changjiang, Liu, Yuhang, Yu, Yifeng, Zhang, Dong, Yu, Aixi. 2022. Identification of Up-Regulated ANXA3 Resulting in Fracture Non-Union in Patients With T2DM. In Frontiers in endocrinology, 13, 890941. doi:10.3389/fendo.2022.890941. https://pubmed.ncbi.nlm.nih.gov/35813617/
7. Chen, Yuanyuan, Di, Muping, Tang, Yan, Xiang, Tong, Xia, Jianchuan. 2024. Epstein-Barr virus causes vascular abnormalities in epithelial malignancies through upregulating ANXA3-HIF-1α-VEGF pathway. In Oncogene, 43, 2143-2159. doi:10.1038/s41388-024-03061-w. https://pubmed.ncbi.nlm.nih.gov/38778160/
8. Jiang, Jie, Zhan, Xinli, Qu, Haishun, Zhu, Jichong, Liu, Chong. 2022. Upregulated of ANXA3, SORL1, and Neutrophils May Be Key Factors in the Progressionof Ankylosing Spondylitis. In Frontiers in immunology, 13, 861459. doi:10.3389/fimmu.2022.861459. https://pubmed.ncbi.nlm.nih.gov/35464477/
9. Jacintho, Bruna Cardoso, Mazetto Fonseca, Bruna de Moraes, Hounkpe, Bidossessi Wilfried, de Paula, Erich Vinicius, Orsi, Fernanda Andrade. 2023. Evaluation of a gene signature related to thrombotic manifestations in antiphospholipid syndrome. In Frontiers in medicine, 10, 1139906. doi:10.3389/fmed.2023.1139906. https://pubmed.ncbi.nlm.nih.gov/37035297/