Inhibition of MDFI attenuates proliferation and glycolysis of Helicobacter pylori-infected gastric cancer cells by inhibiting Wnt/beta-catenin pathway

Cell Biology International(2022)

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摘要
MyoD family inhibitor (MDFI) is a myogenic transcription factor regulatory protein. MDFI has been proven to be upregulated and to promote cell proliferation in colorectal cancer. However, the role of MDFI in gastric cancer (GC) is unclear. In this study, MDFI expression in GC tissues and cell lines was examined by quantitative real-time PCR and western blot. Cell Counting Kit-8 assay, clone formation assay, and 5-ethynyl-2'-deoxyuridine assay were used to evaluate GC cell proliferation. Glycolysis was assessed by measuring glucose consumption and lactate and ATP production using commercial assay kits. Western blot was used to detect the expression levels of glycolytic key proteins and Wnt/beta-catenin pathway proteins. To activate Wnt/beta-catenin signaling, GC cells were treated with CHIR-99021. We found that MDFI expression was increased in GC tumor tissues and cells with a positive correlation with poor survival. Knockdown of MDFI inhibited the increase in GC cell proliferation and glycolysis induced by Helicobacter pylori. Helicobacter pylori infection promoted MDFI expression and activated Wnt/beta-catenin signaling. What is more, activation of the Wnt/beta-catenin pathway remarkably reversed the effect of knocking down MDFI on GC cells. Further studies found that MDFI participated in GC cell proliferation and glycolysis by regulating the Wnt/beta-catenin pathway, thereby affecting the development of GC. In conclusion, we demonstrated for the first time that knockdown of MDFI inhibited the increase in GC cell proliferation and glycolysis by regulating the Wnt/beta-catenin pathway. MDFI may be a new target for the clinical treatment of GC.
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关键词
gastric cancer,glycolysis,Helicobacter pylori,MDFI,Wnt/beta-catenin
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