2. Academic Validation
  3. Transcription Factor E2F4 Promote Proliferation, Migration, and Invasion of Gastric Cancer Cells by transcriptionally activating DSCC1

Transcription Factor E2F4 Promote Proliferation, Migration, and Invasion of Gastric Cancer Cells by transcriptionally activating DSCC1

  • Int J Biol Sci. 2024 Sep 16;20(12):4978-4998. doi: 10.7150/ijbs.99590.
Shantanu Baral 1 2 3 4,  Yantao Yu 4 5,  Qiannan Sun 2 4,  Mingrui Jiang 1 2 3 4,  Ruiqi Li 4 6,  Yifan Cheng 4 6,  Arawker Mubeen Hussein 3,  Youquan Shi 4,  Yongjun Jiang 4,  Dong Tang 2,  Sen Wang 7,  Daorong Wang 1 2 3 4 6 5
Affiliations

Affiliations

  • 1 Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, 225001, P. R. China.
  • 2 Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, 225001, P. R. China.
  • 3 General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou, Jiangsu, 225001, P. R. China.
  • 4 Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou, Jiangsu, 225001, P. R. China.
  • 5 The Yangzhou School of Clinical Medicine of Dalian Medical University. Yangzhou, Jiangsu, 225001, P. R. China.
  • 6 Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, Jiangsu, 225001, P. R. China.
  • 7 Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, P. R. China.
PMID: 39309429 DOI: 10.7150/ijbs.99590
Abstract

Gastric Cancer (GC) ranks as the fifth most common Cancer and the fourth leading cause of cancer-related deaths globally. Despite advancements in molecular profiling, the mechanisms driving GC proliferation and metastasis remain unclear. This study identifies Early 2 Factor 4 (E2F4) as a key transcription factor that promotes GC cell proliferation, migration, and invasion by upregulating DNA Replication and Sister Chromatid Cohesion 1 (DSCC1) expression. Bioinformatics and transcription factor analyses revealed E2F4 as a significant regulator of DSCC1. Functional assays confirmed E2F4's role in enhancing GC cell malignancy in vitro and in vivo. Knockdown and overexpression experiments demonstrated that E2F4 positively regulates DSCC1 at the transcriptional level, with ChIP-qPCR and dual luciferase reporter assays validating the binding sites on the DSCC1 promoter. These findings highlight the E2F4-DSCC1 axis as a potential therapeutic target to mitigate GC progression.

Keywords

DNA Replication and Sister Chromatid Cohesion 1; Early 2 Factor 4; Gastric Cancer; Proliferation; transcription.

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