Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
The Second Affiliated Hospital of University of South China, Hengyang 421001, China.
Aging (Albany NY). 2021 Jun 24;13(12):16043-16061. doi: 10.18632/aging.203130.
HMGA1 protein is an architectural transcription factor that has been implicated in the progression of multiple malignant tumors. However, the role of HMGA1 in the growth and metastasis of gastric cancer (GC) has not yet been elucidated. Here, we show that HMGA1 is overexpressed in GC cells and the high expression of HMGA1 was correlated with worse survival in GC patients using a bioinformatics assay. Functionally, HMGA1 affected the EdU incorporation, colony formation, migration and invasion of GC cells by exogenously increasing or decreasing the expression of HMGA1. Mechanistically, HMGA1 directly bound to the SUZ12 and CCDC43 promoter and transactivated its expression in GC cells. Inhibition of SUZ12 and CCDC43 attenuated the proliferation, migration and invasiveness of HMGA1-overexpressing GC cells . Moreover, both HMGA1 and SUZ12/CCDC43 were highly expressed in cancer cells but not in normal gastric tissues, and their expressions were positively correlated. Finally, a tail vein metastatic assay showed that HMGA1 promoted SUZ12/CCDC43-mediated GC cell metastasis . Our findings suggest that HMGA1 promotes GC growth and metastasis by transactivating SUZ12 and CCDC43 expression, highlighting HMGA1 as a potential prognostic biomarker in the treatment of GC.
HMGA1 蛋白是一种结构转录因子，与多种恶性肿瘤的进展有关。然而，HMGA1 在胃癌（GC）的生长和转移中的作用尚未阐明。在这里，我们通过生物信息学检测显示 HMGA1 在 GC 细胞中过表达，并且 HMGA1 的高表达与 GC 患者的生存预后较差相关。功能上，HMGA1 通过外源增加或减少 HMGA1 的表达，影响 GC 细胞的 EdU 掺入、集落形成、迁移和侵袭。机制上，HMGA1 直接结合到 SUZ12 和 CCDC43 启动子上，并在 GC 细胞中转激活其表达。抑制 SUZ12 和 CCDC43 可减弱 HMGA1 过表达 GC 细胞的增殖、迁移和侵袭能力。此外，HMGA1 和 SUZ12/CCDC43 在癌细胞中高表达而在正常胃组织中不表达，且它们的表达呈正相关。最后，尾静脉转移实验表明，HMGA1 促进了 SUZ12/CCDC43 介导的 GC 细胞转移。我们的研究结果表明，HMGA1 通过反式激活 SUZ12 和 CCDC43 的表达促进 GC 的生长和转移，突出了 HMGA1 作为治疗 GC 的潜在预后生物标志物的潜力。
