Yu Changyun, Zhang Chen, Zhang Qianqian, Zhang Cai, Han Jingjie, Li Jinying
Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Department of Otolaryngology Head and Neck Surgery, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, China.
iScience. 2024 Dec 13;28(1):111590. doi: 10.1016/j.isci.2024.111590. eCollection 2025 Jan 17.
Tripartite motif-containing 47 (TRIM47) is a member of the TRIM family, which has E3 ligase activity and has been demonstrated to be involved in tumor development. In this work, we found that TRIM47 is highly expressed in head and neck squamous cell carcinomas (HNSCC) tissues. TRIM47 overexpression promoted HNSCC cell proliferation. Downregulation of TRIM47 suppressed HNSCC cell proliferation and promoted apoptosis and autophagy. TRIM47 suppression caused cell proliferation inhibition and apoptosis promotion could be reversed by 3-MA, an autophagy inhibitor. In mechanism, TRIM47 interacted with XIAP-associated factor 1 (XAF1), promoting its ubiquitination and degradation. XAF1 promoted HNSCC cell apoptosis and autophagy. TRIM47 overexpression caused cell proliferation promotion and autophagy inhibition could be reversed by XAF1 overexpression. Animal experiments confirmed that the knockdown of TRIM47 inhibits tumor growth . Ultimately, TRIM47 promotes the ubiquitination and degradation of XAF1 and suppresses apoptosis and autophagy to promote the progression of HNSCC.
含三联基序蛋白47（TRIM47）是TRIM家族的成员，具有E3连接酶活性，且已被证明参与肿瘤发展。在本研究中，我们发现TRIM47在头颈部鳞状细胞癌（HNSCC）组织中高表达。TRIM47的过表达促进了HNSCC细胞增殖。TRIM47的下调抑制了HNSCC细胞增殖，并促进了细胞凋亡和自噬。TRIM47的抑制导致细胞增殖受抑制，而细胞凋亡促进作用可被自噬抑制剂3-甲基腺嘌呤（3-MA）逆转。机制上，TRIM47与X连锁凋亡抑制蛋白相关因子1（XAF1）相互作用，促进其泛素化和降解。XAF1促进HNSCC细胞凋亡和自噬。TRIM47的过表达导致的细胞增殖促进和自噬抑制可被XAF1的过表达逆转。动物实验证实，敲低TRIM47可抑制肿瘤生长。最终，TRIM47促进XAF1的泛素化和降解，抑制细胞凋亡和自噬，从而促进HNSCC的进展。
