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 in vitro. 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 in vivo. 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.

中文翻译：

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HMGA1通过反式激活SUZ12和CCDC43的表达促进胃癌的生长和转移

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）生长和转移中的作用尚未阐明。在这里，我们显示 HMGA1 在 GC 细胞中过度表达，并且 HMGA1 的高表达与使用生物信息学分析的 GC 患者较差的存活率相关。在功能上，HMGA1 通过外源性增加或减少 HMGA1 的表达来影响 GC 细胞的 EdU 掺入、集落形成、迁移和侵袭。从机制上讲，HMGA1 直接与 SUZ12 和 CCDC43 启动子结合并激活其在 GC 细胞中的表达。SUZ12和CCDC43的抑制减弱HMGA1过表达GC细胞的增殖，迁移和侵袭体外. 此外，HMGA1和SUZ12/CCDC43均在癌细胞中高表达，但在正常胃组织中不高表达，且二者表达呈正相关。最后，尾静脉转移试验表明 HMGA1 促进了 SUZ12/CCDC43 介导的 GC 细胞体内转移。我们的研究结果表明 HMGA1 通过反式激活 SUZ12 和 CCDC43 表达促进 GC 生长和转移，突出 HMGA1 作为治疗 GC 的潜在预后生物标志物。