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HNF4A promotes tumor progression in gastric cancer by transcriptional activation of KIF2C

  • 1Department of General Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1 Minde Road, Donghu District, Nanchang, 330006, Jiangxi Province, China.
  • 2Jiangxi Province Key Laboratory of Molecular Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, China.
  • 3Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China.
  • 4Department of General Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1 Minde Road, Donghu District, Nanchang, 330006, Jiangxi Province, China. DocLinXin@126.com.
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June 14, 2025

Abstract

Hepatocyte nuclear factor 4A (HNF4A) is a core transcription factor that plays an important role in tumor progression. However, the regulatory mechanisms in gastric cancer remain unclear. In this study, we employed a bioinformatics-driven approach and combined it with cellular and animal experiments to investigate the regulatory mechanisms of HNF4A in gastric cancer. We identified kinesin family member 2C (KIF2C) as a novel downstream target of HNF4A and observed that both HNF4A and KIF2C were significantly upregulated in gastric cancer tissues. Knockdown of HNF4A or KIF2C inhibited the proliferation, migration, and invasion abilities of gastric cancer cells, while overexpression of KIF2C rescued these abilities of sh-HNF4A in gastric cancer cells. Mechanistically, HNF4A and KIF2C were found to colocalize in the nucleus, with HNF4A directly binding to the KIF2C promoter. Further analysis identified BS2 (-1381 ~ -1368) and BS3 (-715 ~ -700) as the core binding regions. In vivo experiments demonstrated that knockdown HNF4A inhibited tumor growth in BALB/c nude mice, and overexpression of KIF2C promoted tumor growth. In conclusion, HNF4A is an oncogene that promotes the proliferation, migration, and invasion of gastric cancer cells. Our study suggests that HNF4A can transcriptionally activate KIF2C and that the HNF4A-KIF2C axis may be a potential therapeutic target for gastric cancer.

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