2. Academic Validation
  3. FGF19 promotes nasopharyngeal carcinoma progression by inducing angiogenesis via inhibiting TRIM21-mediated ANXA2 ubiquitination

FGF19 promotes nasopharyngeal carcinoma progression by inducing angiogenesis via inhibiting TRIM21-mediated ANXA2 ubiquitination

  • Cell Oncol (Dordr). 2023 Oct 2. doi: 10.1007/s13402-023-00868-9.
Si Shi # 1 2,  Qicheng Zhang # 1 2,  Kaiwen Zhang 1 2,  Wenhui Chen 1 2,  Haijing Xie 1 2,  Si Pan 1 2,  Ziyi Xue 1 2,  Bo You 3 4,  Jianmei Zhao 5,  Yiwen You 6 7
Affiliations

Affiliations

  • 1 Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, Jiangsu Province, China.
  • 2 Institute of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China.
  • 3 Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, Jiangsu Province, China. youbo19891014@163.com.
  • 4 Institute of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China. youbo19891014@163.com.
  • 5 Department of Paediatrics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China. zjmheart@163.com.
  • 6 Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, Jiangsu Province, China. youyiwen_nantong@163.com.
  • 7 Institute of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China. youyiwen_nantong@163.com.
  • # Contributed equally.
PMID: 37782406 DOI: 10.1007/s13402-023-00868-9
Abstract

Purpose: Nasopharyngeal carcinoma (NPC) has characteristics of high invasion and early metastasis. Most NPC patients present with locoregionally advanced illness when first diagnosed. Therefore, it is urgent to discover NPC biomarkers. Fibroblast Growth Factor 19 (FGF19) plays a role in various physiological or pathological processes, including Cancer. In this research, we discovered the importance of FGF19 in NPC, and clarified its role in tumour angiogenesis.

Methods: Western blotting, immunohistochemistry and ELISA were used to investigate FGF19 expression in NPC. Then we took CCK8, colony formation, Transwell and wound healing assays to identify the influence of FGF19 on NPC malignant behaviours. The proliferative and metastatic capacity of FGF19 were evaluated in nude mice and zebrafish. The role of FGF19 in angiogenesis was investigated by tube formation and Matrigel plug angiogenesis assays. We then evaluated the variation in Annexin A2(ANXA2) levels with the treatment of FGF19. Lastly, co-immunoprecipitation and ubiquitination assays were performed to identify the mechanisms involved.

Results: FGF19 levels were elevated in tissues and serum of NPC patients and were associated with poor clinical stages. High expression of FGF19 promoted NPC malignant behaviours. In particular, FGF19 expression was correlated with microvessel density in tissues and NPC-derived FGF19 could accelerate angiogenesis in vitro and in vivo. Mechanistically, FGF19 influenced ANXA2 expression to promote angiogenesis. Moreover, tripartite motif-containing 21(TRIM21) interacted with ANXA2 and was responsible for ANXA2 ubiquitination.

Conclusion: FGF19 promoted NPC angiogenesis by inhibiting TRIM21-mediated ANXA2 ubiquitination. It may serve as a noninvasive biomarker for NPC and provides new insights for therapy.

Keywords

ANXA2; Angiogenesis; FGF19; Nasopharyngeal carcinoma; TRIM21.

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