Research Paper Volume 13, Issue 12 pp 16043—16061
HMGA1 promotes gastric cancer growth and metastasis by transactivating SUZ12 and CCDC43 expression
- 1 Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
- 2 Department of Gastroenterology, Longgang District People’s Hospital, Shenzhen 518172, China
- 3 Department of Gastroenterology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China
- 4 The Second Affiliated Hospital of University of South China, Hengyang 421001, China
Received: December 15, 2020 Accepted: May 13, 2021 Published: June 24, 2021https://doi.org/10.18632/aging.203130
How to Cite
Copyright: © 2021 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.