Department of Gynecology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450000, China.
Department of Gynecology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450000, China.
Arch Biochem Biophys. 2022 Oct 15;728:109372. doi: 10.1016/j.abb.2022.109372. Epub 2022 Jul 31.
Tripartite motif containing 37 (TRIM37) was reported to function as a tumor promoter in the development of various cancers. However, the biological role of TRIM37 in ovarian cancer (OC) was still unclear. Expressions of TRIM37 and HUWE1 were detected by qRT-PCR and western blotting in OC cells. Cell proliferation was evaluated by CCK-8 assay and colony formation assay. Cell migration and invasion capabilities were examined by wound healing and transwell assay. Flow cytometry and western blotting were performed to measure cell apoptosis. Wnt/β-catenin pathway and the expression of c-Myc were identified by qRT-PCR and western blotting. The binding of TRIM37 and HUWE1 was predicted by STRING database and verified by co-immunoprecipitation. In addition, a xenograft mouse model was established to evaluate the effects of TRIM37 and HUWE1 on tumor growth and c-MYC expression in vivo. The present study revealed that TRIM37 expression was upregulated in OC tissues and cells. TRIM37 silencing inhibited OC cell migration and invasion, promoted OC cell apoptosis, and blocked Wnt/β-catenin signaling pathway, as well as suppressing c-MYC protein expression. Mechanistic studies suggested that TRIM37 binds to HUWE1. HUWE1 was upregulated in OC cells and TRIM37 promoted the c-MYC expression through targeting HUWE1. Animal experiments showed that TRIM37 silencing significantly repressed the tumor growth and c-MYC protein level, but HUWE1 overexpression reversed the effects of TRIM37 knockdown on mice with OC. Our findings revealed that TRIM37 accelerated the progression of OC and promoted c-MYC expression by binding to HUWE1, which provides therapeutic targets for OC treatment.
三结构域蛋白 37（TRIM37）被报道在各种癌症的发展中作为肿瘤促进剂发挥作用。然而，TRIM37 在卵巢癌（OC）中的生物学作用尚不清楚。通过 qRT-PCR 和 Western blot 检测 OC 细胞中 TRIM37 和 HUWE1 的表达。通过 CCK-8 assay 和集落形成 assay 评估细胞增殖。通过划痕愈合和 Transwell assay 检测细胞迁移和侵袭能力。通过流式细胞术和 Western blot 检测细胞凋亡。通过 qRT-PCR 和 Western blot 鉴定 Wnt/β-catenin 通路和 c-Myc 的表达。通过 STRING 数据库预测 TRIM37 和 HUWE1 的结合，并通过共免疫沉淀验证。此外，建立异种移植小鼠模型以评估 TRIM37 和 HUWE1 对体内肿瘤生长和 c-MYC 表达的影响。本研究表明，TRIM37 在 OC 组织和细胞中表达上调。TRIM37 沉默抑制 OC 细胞迁移和侵袭，促进 OC 细胞凋亡，并阻断 Wnt/β-catenin 信号通路，同时抑制 c-MYC 蛋白表达。机制研究表明，TRIM37 与 HUWE1 结合。HUWE1 在 OC 细胞中上调，TRIM37 通过靶向 HUWE1 促进 c-MYC 表达。动物实验表明，TRIM37 沉默显著抑制 OC 肿瘤生长和 c-MYC 蛋白水平，但 HUWE1 过表达逆转了 TRIM37 敲低对 OC 小鼠的影响。我们的研究结果表明，TRIM37 通过与 HUWE1 结合加速 OC 的进展并促进 c-MYC 表达，为 OC 治疗提供了治疗靶点。
