1. Silencing AHNAK promotes nasopharyngeal carcinoma progression by upregulating the ANXA2 protein.
- Author
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Lu X, Mei Y, Fan C, Chen P, Li X, Zeng Z, Li G, Xiong W, Xiang B, and Yi M
- Subjects
- Humans, Animals, Cell Line, Tumor, Female, Male, Neoplasm Proteins metabolism, Neoplasm Proteins genetics, Membrane Proteins metabolism, Membrane Proteins genetics, Gene Expression Regulation, Neoplastic, Middle Aged, Gene Silencing, Mice, Mice, Inbred BALB C, Cell Proliferation genetics, Annexin A2 metabolism, Annexin A2 genetics, Nasopharyngeal Carcinoma genetics, Nasopharyngeal Carcinoma pathology, Nasopharyngeal Carcinoma metabolism, Up-Regulation genetics, Nasopharyngeal Neoplasms genetics, Nasopharyngeal Neoplasms pathology, Nasopharyngeal Neoplasms metabolism, Mice, Nude, Disease Progression
- Abstract
Purpose: Nasopharyngeal carcinoma (NPC) is an aggressive head and neck disease with a high incidence of distant metastases. Enlargeosomes are cytoplasmic organelles marked by, desmoyokin/AHNAK. This study aimed to evaluate the expression of AHNAK in NPC and its effect on enlargeosomes and to investigate the correlation between AHNAK expression levels and clinical NPC patient characteristics., Methods: Primary nasopharyngeal carcinoma (NPC) and NPC specimens were evaluated by analyzing public data, and immunohistochemistry. Systematic in vitro and in vivo experiments were performed using different NPC-derived cell lines and mouse models., Results: In this study, we detected AHNAK and Annexin A2(ANXA2), a protein coating the surface of enlargeosomes, in NPC samples. We found that AHNAK was down-regulated. Down-regulation of AHNAK was associated with poor overall survival in NPC patients. Moreover, transcription factor FOSL1-mediated transcriptional repression was responsible for the low expression of AHNAK by recruiting EZH2. Whereas Annexin A2 was upregulated in human NPC tissues. Upregulation of Annexin A2 was associated with lymph node metastasis and distant metastasis in NPC patients. Functional studies confirmed that silencing of AHNAK enhanced the growth, invasion, and metastatic properties of NPC cells both in vitro and in vivo. In terms of mechanism, loss of AHNAK led to an increase of annexin A2 protein level in NPC cells. Silencing ANXA2 restored NPC cells' migrative and invasive ability upon loss of AHNAK., Conclusion: Here, we report AHNAK as a tumor suppressor in NPC, which may act through annexin A2 oncogenic signaling in enlargeosome, with potential implications for novel approaches to NPC treatment., (© 2023. Springer Nature Switzerland AG.)
- Published
- 2024
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