Department of Stomatology, Affiliated Hospital of Jining Medical University, No. 89, Guhuai Road, Jining, 272000, Shandong, China; Postdoctoral Mobile Station of Shandong University of Traditional Chinese Medicine, No. 4655, Daxue Road, Changqing District, Jinan, 250399, Shandong, China.
Department of Stomatology, Affiliated Hospital of Jining Medical University, No. 89, Guhuai Road, Jining, 272000, Shandong, China.
Biochem Biophys Res Commun. 2023 Oct 20;678:165-172. doi: 10.1016/j.bbrc.2023.08.030. Epub 2023 Aug 18.
The aberrant expression of TRIM32, an E3 ubiquitin ligase, has been identified in multiple malignant cancer types. Nevertheless, the functional roles and detailed mechanisms of TRIM32 in oral squamous cell carcinoma (OSCC) remain to be elucidated. Here, we investigated TRIM32 expression and its functional role in OSCC. TRIM32 expression was consistently elevated in OSCC tissues, particularly in samples from patients with advanced clinical grades. Functionally, silencing TRIM32 dampened OSCC cell growth, migration and invasion. Additionally, a xenograft tumor model suggested that TRIM32 knockdown suppressed in vivo OSCC tumor growth and lung metastasis formation. Mechanistically, we discovered that TRIM32 directly bound to the FBP2 protein via mass spectrometry and co-immunoprecipitation. TRIM32 could interact with FBP2 and accelerates its degradation, eventually enhancing glycolysis in OSCC cell lines. Importantly, rescue assays demonstrated that FBP2 silencing could at least partially offset the tumor-suppressive and aerobic glycolysis inhibition effect induced by TRIM32 knockdown. Thus, our findings demonstrate that TRIM32 plays a crucial role in promoting tumor growth and enhancing glycolysis through FBP2 inhibition. Given OSCC is associated with increased glycolysis levels, our study suggests potential therapeutic targets for OSCC treatment.
TRIM32 是一种 E3 泛素连接酶，其异常表达已在多种恶性肿瘤类型中被鉴定出来。然而，TRIM32 在口腔鳞状细胞癌（OSCC）中的功能作用和详细机制仍有待阐明。在这里，我们研究了 TRIM32 在 OSCC 中的表达及其功能作用。TRIM32 的表达在 OSCC 组织中持续升高，特别是在临床分级较高的患者样本中。功能上，沉默 TRIM32 抑制了 OSCC 细胞的生长、迁移和侵袭。此外，异种移植肿瘤模型表明，TRIM32 敲低抑制了体内 OSCC 肿瘤的生长和肺转移形成。在机制上，我们通过质谱和共免疫沉淀发现 TRIM32 可直接与 FBP2 蛋白结合。TRIM32 可以与 FBP2 相互作用并加速其降解，最终增强 OSCC 细胞系中的糖酵解。重要的是，挽救实验表明，沉默 FBP2 至少可以部分抵消由 TRIM32 敲低引起的肿瘤抑制和有氧糖酵解抑制作用。因此，我们的研究结果表明，TRIM32 通过抑制 FBP2 在促进肿瘤生长和增强糖酵解方面发挥关键作用。鉴于 OSCC 与糖酵解水平升高有关，我们的研究为 OSCC 治疗提供了潜在的治疗靶点。
