ORIGINAL RESEARCH article
Front. Oncol.
Sec. Neuro-Oncology and Neurosurgical Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1550961
Human Annexin A5 promotes glioma progression by targeting the MAPK/CD44 pathway
Provisionally accepted- Zhejiang Hospital, Hangzhou, China
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Background: Gliomas are the most common intracranial malignant tumors. In this study, we aimed to identify the hub genes and investigate the pathophysiological significance of ANXA5 in glioma. Methods: The differentially expressed genes (DEGs) between tumor and adjacent tissues from glioma patients were acquired from the Gene Expression Omnibus (GEO) database. Functional enrichment analysis and protein-protein interaction (PPI) network construction of overlapping DEGs were performed. The GEPIA and CGGA databases were used to explore hub gene expression. The effect of hub genes on prognosis and tumor-infiltrating immune cells was analyzed via GEPIA, CGGA, and TIMER2 databases. Additionally, ANXA5 expression was measured by qRT-PCR and Western blotting. The effects of ANXA5 were assessed by CCK-8, colony formation, Transwell, and flow cytometry assays. Moreover, the roles of ANXA5 were identified in vivo. Results: The DEGs were enriched in cell surface receptor signaling pathway, immune response, and MAPK signaling pathway. The selected hub genes were included ANXA5, STAT1, CD44, CAV1, ANXA2, and MAPT. Among them, expression of ANXA5, STAT1, CD44, CAV1, and ANXA2 was strongly correlated with patient prognosis and was also involved in the tumor microenvironment. Furthermore, ANXA5 knockdown significantly inhibited the migration and proliferation of glioma cells in vitro and in vivo. Meanwhile, we found that the expression of CD44 was monitored by ANXA5, and ANXA5 promoted the migration and proliferation of glioma cells via the MAPK/CD44 pathway. Conclusion: Taken together, our data showed that ANXA5 could contribute to cell proliferation and metastasis of glioma by targeting the MAPK/CD44 axis.
Keywords: Glioma, Anxa5, CD44, MAPK, Gene Expression Omnibus
Received: 13 Jan 2025; Accepted: 31 May 2025.
Copyright: © 2025 Liu, Xiong, Sun, Wang, Zhu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: ChuanChuan Li, Zhejiang Hospital, Hangzhou, China
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