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 and . 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.
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http://dx.doi.org/10.7150/ijbs.99590 | DOI Listing |
Planta
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State Key Laboratory of Crop Gene Resources and Breeding, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100081, China.
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Department of Toxicology, School of Public Health, Hebei Medical University, Shijiazhuang, 050017, PR China; Hebei Key Laboratory of Environment and Human Health, Hebei Province, Shijiazhuang, 050017, PR China. Electronic address:
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Institute of Medical Science, Ajou University School of Medicine, Suwon, Gyeonggi 16499, Republic of Korea; Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Gyeonggi 16499, Republic of Korea. Electronic address:
Oxidative stress caused by reactive oxygen species (ROS) and superoxides is linked to various cancer-related biological events. Extracellular superoxide dismutase (SOD3), an antioxidant enzyme that removes superoxides, contributes to redox homeostasis and has the potential to regulate tumorigenesis. Histone deacetylase 6 (HDAC6), a major HDAC isoform responsible for mediating the deacetylation of non-histone protein substrates, also plays a role in cancer progression.
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Department of Chemistry and Biochemistry, University of California Merced, Merced, 95343; Department of Chemistry, Syracuse University, Syracuse, 13244.
Transcription factor proteins bind to specific DNA promoter sequences and initiate gene transcription. These proteins often contain intrinsically disordered activation domains (ADs) that regulate their transcriptional activity. Like other disordered protein regions, ADs do not have a fixed three-dimensional structure and instead exist in an ensemble of conformations.
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