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The Higher Expressions Of MAGOH And MAGOHB Identified By Proteomics And Their Related Functions In Gastric Cancer

Posted on:2020-02-29Degree:MasterType:Thesis
Country:ChinaCandidate:Y ZhouFull Text:PDF
GTID:2404330578978540Subject:Oncology
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BackgroundGastric cancer is one of the most malignant tumors,and its morbidity and mortality rank among the top five in the world.In China,because the patient diagnosed as gastric cancer are often in the advanced stage,and the effect of existing treatments is limited,it is urgent to explore its underlying mechnisms and find new biomarkers and possible therapeutic targets.In recent years,due to the emergence and rapid development of mass spectrometry,proteomics has been widely applied in cancer research,providing a new powerful means for exploring the pathogenesis of cancer and finding early diagnostic biomarkers and therapeutic targets.In this study,we used mass spectrometry and label-free quantitative proteomics to explore the new mechnism and potential biomarkers for the diagnosis and therapy of gastric cancer.MethodsIn this study,14 gastric cancer tissues and 6 normal gastric tissues were collected and analysized by label-free quantitative proteomics.The bio-informatics function annotations were performed on these differentially expressed proteins.Subsequently,candidate biomarkers were verified by western blot and immunehistochemistry.Finally,using small interfering RNA,CCK8 assay,flow cytometry and Western blot to evaluate the role of candidate biomarkers in cell proliferation and apoptosis.ResultsThrough a series of experiments,we obtained the following results.First,we analyzed up to 3400 proteins and 294 differentially expressed proteins,and bio-informatics analysis revealed that the enrichment of nucleic acid-binding proteins was particularly prominent,which were also related to the process of RNA synthesis,splicing and metabolism.Then,we used Western blot and immunohistochemistry to verify that the expressions of MAGOH and MAGOHB were higher in gastric cancer tissues than normal gastric tissues.Finally,after down-regulating MAGOH and MAGOHB together in the gastric cancer cell,the cell proliferation was greatly inhibited,the rate of cell apoptosis was significantly increased,and the related proteins on the ERK1/2 signaling pathway were significantly decreased.ConclusionWe found that MAGOH and MAGOHB proteins were highly expressed in gastric cancer tissues by lable-free quantitative proteomics.Both two proteins cooperate in regulating the proliferation and apoptosis of gastric cancer cells,and are expected to become new biomarkers for clinical diagnosis and therapeutic of gastric cancer.
Keywords/Search Tags:Gastric cancer, Label-free quantitative proteomics, MAGOH、MAGOHB protein, Cell proliferation and apoptosis
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