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The Effects Of MXRA7 On Proliferation,Migration And Invasion Of Esophageal Cancer Cells And Its Mechanism Research

Posted on:2021-03-29Degree:MasterType:Thesis
Country:ChinaCandidate:X X SunFull Text:PDF
GTID:2404330602487054Subject:Biochemistry and Molecular Biology
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Esophageal cancer is a common gastrointestinal tumor,and higher incidence in China than other countries.Based on histopathological classification,it can be divided into esophageal adenocarcinoma and esophageal squamous cell carcinoma,which is the most common kind in China.Because the early symptoms of esophageal cancer are hidden and early diagnosis is difficult,most of esophageal cancer are in the high advanced stages once discovered..While The esophageal cancer patients diagnosed with early state have favorable clinical outcome,so the 5-year survival rate of patients is less than 20%.It is essential to develop novel prognostic biomarkers to investigate the molecular mechanism of esophageal cancer.In current study,we found that the expression of MXRA7(matrix remodeling associated 7)protein presents different distributions or changes in clinical tumor tissues,and has different distribution patterns in the cytoplasm and nucleus of normal cells or tumor cells,and it can be involved in the extracellular Extracellular matrix composition and remodeling,suggesting that MXRA7 maybe plays a vital role in tumorigenesis.Oncomine database forecasts that MXRA7 is significantly expressed in esophageal cancer tissues;and by immunohistochemical staining(IHC)analysis of human esophageal cancer pathological tissues and normal human tissues,we found that the MXRA7 gene is partly highly expressed in human esophageal cancer tissues,but low expressed in normal tissues,suggesting that MXRA7 is involved in the occurrence of esophageal cancerIn the first part of the study,the XRA7 gene silencing and overexpression esophageal cancer cells were constructed to explore the role of MXRA7 gene in esophageal cancer cells.CCK-8 experiment results showed that the silencing of MXRA7 gene significantly inhibited the proliferation ability of OE33,BIC-1 and TE-1 cells;while overexpression of MXRA7 gene increased the proliferation ability of OE33 cells.The transwell chamber was used to detect the migration and invasion ability of cells,and the results showed that the silencing of MXRA7 gene significantly inhibited the migration and invasion ability of OE33 and BIC-1 cells,but improved the migration and invasion ability of TE-1 cells;while overexpression of MXRA7 gene improved the migration and invasion ability of OE33 cells.In addition,the cell cycle results showed that the silencing of the MXRA7 gene changed the cell cycle of BIC-1 and TE-1 cells,but it did not affect the cell cycle of OE33 cells.In the second part of the study,the effects of MXRA7 on the tumor-forming ability of OE33 cells were explored through the tumor-bearing model.The results showed that the silencing of the MXRA7 gene significantly inhibited the tumorigenic ability of OE33 cells in nude mice.In the third part of the study,the transcriptome sequencing and western blot methods were used to explore the potential mechanism of MXRA7.The results showed that in OE33 and TE-1 cells,the silencing of MXRA7 gene significantly increased the phosphorylation level of JNK and p38 proteins in the MAPK signaling pathway,while the phosphorylation level of AKT protein was significantly decreased.This indicated that MXRA7 gene may affect the proliferation,migration,invasion and tumorigenesis of esophageal cancer cells by regulating the MAPK signaling pathwayIn summary,we explored the role of MXRA7 gene in esophageal cancer from three aspects of cell experiments,animal models and molecular mechanisms.And we also figured out whether it can be a potential target of clinical treatment of esophageal cancer,which can provide part of the theoretical basis for the clinical diagnosis and treatment of esophageal cancer.
Keywords/Search Tags:MXRA7, Esophageal cancer, Tumorigenesis, Cell proliferation, Cell migration, Cell invasion
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