Anxa3, or annexin A3, is a member of the annexin family. It is involved in multiple biological processes and associated with various signaling pathways, such as the AKT-GSK3β-β-catenin pathway. It plays important roles in cell function regulation, and its abnormal expression is linked to the development of numerous diseases, making it a potential target for disease treatment [1-10].

In laryngeal squamous cell carcinoma, ANXA3 in tumor-associated macrophages promotes M2-like polarization via the AKT-GSK3β-β-catenin pathway. ANXA3-rich exosomes from these macrophages inhibit ferroptosis in laryngeal cancer cells through an ATF2-CHAC1 axis, which is associated with lymphatic metastasis [1]. In cervical cancer, ANXA3 is highly expressed, and its knockdown inhibits cell cycle progression and increases cisplatin sensitivity. Its expression is positively correlated with YAP1 [2]. ANXA3 may be a novel diagnostic biomarker for sepsis, as its transcription was significantly higher in the peripheral blood of septic mice compared to healthy controls [3]. In colon cancer, ANXA3 expression is upregulated by hypoxia-inducible factor 1-alpha (HIF-1α) and contributes to tumor growth [4]. In ischemic stroke, ANXA3 was identified as a possible pyroptosis-related gene marker, and its silencing alleviated the expression of pyroptosis-related factors [5]. In HCV infection, ANXA3 is an important host factor, and proximity labeling revealed a novel LARP1 function in viral entry [6]. In lung cancer, knocking down ANXA3 inhibits the resistance of lung cancer cells to oxaliplatin [7]. In intracranial aneurysm, ANXA3 silencing can rescue vascular smooth muscle cell function by inhibiting the phosphorylation and activation of the JNK signaling pathway [8]. Epstein-Barr virus upregulates the ANXA3-HIF-1α-VEGF pathway, causing vascular abnormalities in epithelial malignancies, and ANXA3 blockade may be a potential therapy [9]. The 33-kDa ANXA3 isoform contributes to hepatocarcinogenesis by modulating the ERK, PI3K/Akt-HIF, and intrinsic apoptosis pathways [10].

In conclusion, Anxa3 is involved in diverse biological functions, including cell polarization, ferroptosis regulation, cell cycle progression, and apoptosis. Its abnormal expression is associated with multiple diseases such as various cancers, sepsis, and ischemic stroke. Studies on Anxa3, especially through gene-based models like knockdown experiments, help in understanding disease mechanisms and developing potential therapeutic strategies for these diseases.

References:

1. Xu, Licheng, Li, Wenjing, Liu, Danxi, Liu, Ming, Tian, Linli. . ANXA3-Rich Exosomes Derived from Tumor-Associated Macrophages Regulate Ferroptosis and Lymphatic Metastasis of Laryngeal Squamous Cell Carcinoma. In Cancer immunology research, 12, 614-630. doi:10.1158/2326-6066.CIR-23-0595. https://pubmed.ncbi.nlm.nih.gov/38393971/

2. 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/

3. Zhang, Jing-Xiang, Xing, Xin-Hao, Lu, Ren-Yi, Zhao, Qing-Jie, Wang, Yan. 2024. ANXA3 as a novel biomarker for sepsis diagnosis: Evidence from integrative WGCNA analysis. In Heliyon, 10, e38608. doi:10.1016/j.heliyon.2024.e38608. https://pubmed.ncbi.nlm.nih.gov/39430518/

4. Du, Kunli, Ren, Jiahui, Fu, Zhongxue, Zheng, Jianyong, Li, Xing. . ANXA3 is upregulated by hypoxia-inducible factor 1-alpha and promotes colon cancer growth. In Translational cancer research, 9, 7440-7449. doi:10.21037/tcr-20-994. https://pubmed.ncbi.nlm.nih.gov/35117344/

5. 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/

6. Bley, Hanna, Krisp, Christoph, Schöbel, Anja, Gerold, Gisa, Herker, Eva. 2024. Proximity labeling of host factor ANXA3 in HCV infection reveals a novel LARP1 function in viral entry. In The Journal of biological chemistry, 300, 107286. doi:10.1016/j.jbc.2024.107286. https://pubmed.ncbi.nlm.nih.gov/38636657/

7. Jin, Y-F, Huang, Y-T, Chen, P-F. . ANXA3 deletion inhibits the resistance of lung cancer cells to oxaliplatin. In European review for medical and pharmacological sciences, 24, 3741-3748. doi:10.26355/eurrev_202004_20838. https://pubmed.ncbi.nlm.nih.gov/32329851/

8. Wang, Yang, Wang, Chun, Yang, Qi, Cheng, Yan-Li. 2019. ANXA3 Silencing Ameliorates Intracranial Aneurysm via Inhibition of the JNK Signaling Pathway. In Molecular therapy. Nucleic acids, 17, 540-550. doi:10.1016/j.omtn.2019.06.005. https://pubmed.ncbi.nlm.nih.gov/31362241/

9. 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/

10. Guo, Chunmei, Li, Nannan, Dong, Chengyong, Liu, Shuqing, Sun, Ming-Zhong. 2020. 33-kDa ANXA3 isoform contributes to hepatocarcinogenesis via modulating ERK, PI3K/Akt-HIF and intrinsic apoptosis pathways. In Journal of advanced research, 30, 85-102. doi:10.1016/j.jare.2020.11.003. https://pubmed.ncbi.nlm.nih.gov/34026289/