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Enolase 1 Regulates Gastric Cancer Progression through the Electron Transfer Flavoprotein Dehydrogenase Gene
Vol 37, Issue 8, 2023
Abstract
Background: Gastric cancer (GC) remains the second most common cause of cancer-related death worldwide. The prognosis is dismal, with an average 5-year survival rate of less than 20%. This study aimed to explore the molecular mechanism of enolase 1 (ENO1) in the progression of GC by regulating the electron transfer flavoprotein dehydrogenase (ETFDH) signaling pathway. Methods: siRNA transfection was used to knock down ENO1/ETFDH in MKN45 and HGC27 cells. Cell Counting Kit-8 (CCK-8) assay, cell colony formation, and Transwell experiments were used to determine the role of ENO1 in GC cell proliferation and migration. The expression levels of mRNAs and proteins were quantified using RT-qPCR and western blot. Results: In this study, we identified a new ENO1/ETFDH axis involved in the progression of GC. ENO1 adversely regulated the expression of electron transfer flavoprotein dehydrogenase (ETFDH) in GC cells by regulating the stability of ETFDH mRNA. We then determined the impact of ETFDH on GC cell proliferation and migration in vitro. The results of CCK-8 assay, cell colony formation, and Transwell experiment all demonstrated that GC cell proliferation and migration were enhanced following ETFDH knockdown (p < 0.05), while GC cell growth was decreased by ETFDH overexpression (p < 0.05). The tumor suppressor function of ETFDH on GC development in vivo was also demonstrated by tumor xenograft models (p < 0.05). Conclusions: Our study suggests that the ENO1/ETFDH pathway may be a new target of GC treatment and that adjusting the ratio of ENO1 to ETFDH expression may be beneficial.
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Copyright (c) 2023 Hui Qiao, Na Wang, Quanlin Guan, Peng Xie, Xiangkai Li
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Medical Genetics, University of Torino Medical School, Italy

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy