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The Role Of GALNT6 In Proliferation And Apoptosis Of Lung Adenocarcinoma And Related Mechanisms

Posted on:2021-01-27Degree:MasterType:Thesis
Country:ChinaCandidate:J X HaoFull Text:PDF
GTID:2404330602992659Subject:Internal Medicine
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Background: Lung cancer is the leading cause of cancer-related deaths worldwide.According to statistics in 2019,lung cancer newly diagnosed cases accounted for 13% of all newly diagnosed cancers,and lung cancer deaths in men and women accounted for 24% and 23% of all cancer deaths,respectively.Lung cancer has a poor prognosis,with more than half of people diagnosed with lung cancer dying within one year of diagnosis and a 5-year survival rate of less than 18%.According to histology,there are two main subtypes of lung cancer: small cell lung cancer and non-small cell lung cancer(NSCLC),which account for 15% and 85% of all lung cancers,respectively.The current treatment of NSCLC is still early surgery.Some locally advanced cancers are supplemented with chemoradiation and palliative chemotherapy for metastatic tumors.The treatment methods are limited,so it is particularly important to find new targets for lung cancer treatment.The occurrence of tumors is related to the abnormal proliferation and abnormal apoptosis of cells.Under normal circumstances,cell proliferation and apoptosis are coordinated with each other to maintain a dynamic balance.There is evidence that defects in apoptosis can lead to cancer or autoimmunity.Cancer has also been reported as an example of dysfunction of normal mechanisms of cell cycle regulation,excessive cell proliferation,or decreased cell removal rates.Some people think that inhibiting apoptosis during canceration can play an important role in the treatment of certain cancers.Tumor cells can use a variety of molecular mechanisms to regulate cell proliferation and apoptosis.Polypeptide N-acetylgalactosyltransferase-6(GALNT6)is a glycosyltransferase that participates in the initial step of mucin-type O-glycosylation modification,catalyzing the binding of Gal NAc to O-glycosylation is formed on the side chains of the protein serine or threonine.There is evidence that GALNT6 is abnormally expressed in a variety of tumor clinical samples and tissues,which causes changes in tumor cell proliferation,apoptosis,and metastasis.Therefore,GALNT6 can be used as a potential marker for tumorigenesis,development and prognosis.Many studies have shown that GALNT6 affects the occurrence and development of tumors by promoting substrate abnormal glycosylation in a variety of tumors.However,in the existing studies,the role of GALNT6 on proliferation and apoptosis in lung adenocarcinoma and the O-glycosylated substrate of GALNT6 are unclear.Therefore,it is still unclear how GALNT6 affects the occurrence and development of tumors.At present,the molecular mechanism by which GALNT6 affects the proliferation and apoptosis of lung cancer cells is unclear.This study explored the effect of GALNT6 on cell proliferation,apoptosis,and the mechanism of action by reducing the expression of GALNT6 in lung adenocarcinoma cells.With a view to providing new ideas for the diagnosis and treatment of lung cancer.Methods: In this study,we first used Western Blot technology to detect the expression of GALNT6 in lung adenocarcinoma cell lines;Then,we studied the effects of GALNT6 expression on the proliferation and apoptosis of lung adenocarcinoma cells by Western Blot,CCK-8 experiments,clone formation experiments,apoptosis experiments,and subcutaneous tumor formation experiments in animals;Finally,we revealed its potential molecular mechanisms through co-immunoprecipitation experiments and immunofluorescence,which provided evidence for GALNT6 as a new target for lung cancer diagnosis and treatment.Results: In this study,we first discovered that GALNT6 is highly expressed in lung adenocarcinoma cell lines.After that,we knocked down GALNT6 in lung adenocarcinoma cells.When GALNT6 was knocked down,we found that the proliferation and anti-apoptotic capacity of tumor cells were weakened.Finally,we revealed the molecular mechanism of lung adenocarcinoma cells affecting cell proliferation and apoptosis.Experiments have shown that GALNT6 enhances the stability of the substrate EBP protein through O-glycosylation,which affects tumor proliferation and apoptosis.Conclusions: This study revealed the molecular mechanism of lung adenocarcinoma cells affecting cell proliferation and apoptosis.GALNT6 enhances the stability of the substrate protein EBP through O-glycosylation,which affects the proliferation and apoptosis of lung adenocarcinoma.Therefore,GALNT6 can be used as A promising new target for lung cancer diagnosis and treatment.
Keywords/Search Tags:lung adenocarcinoma, proliferation, apoptosis, Polypeptide N-acetylgalactosyltransferase-6
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