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The Epigenetic Mechanism Of Gene Expression Regulation By TET1-DNMT Network

Posted on:2019-03-19Degree:MasterType:Thesis
Country:ChinaCandidate:Y R LiuFull Text:PDF
GTID:2370330593950052Subject:Biomedical engineering
Abstract/Summary:PDF Full Text Request
Epigenetics refers to the process of changing heritable traits with the genomic sequence that remain constant.Including DNA methylation,histone modification,X chromosome inactivation and so on.The process of DNA methylation is closely related to the development of tumors.DNMT is a DNA methylation transferase that can add a methyl group to a C atom to form 5-methylcytosine,inhibiting tumor suppressor genes by recruiting inhibitors or blocking binding to transcription factors.The TET protein is a dehydroxymethylated protein that can convert 5mC to 5hmC,which in turn reduces to unmethylated carbon atoms.Lung cancer is currently one of the most malignant cancers,and the fatality rate ranks in the top three among malignant tumors.The research topic is based on the non-small cell lung cancer A549,knock down DNMT1 and TET1,through the growth curve,invasion experiments,scratch experiments and other functional experiments to observe its effect on cells,through PCR,Western experiments to observe the interaction.The preliminary result was that DNMT1 promotes the growth of lung cancer cells.The knockdown efficiency of DNMT1 knocked down the cell's invasion efficiency.TET1 inhibits the growth of lung cancer cells.The DOTBLOT experiment verified that the whole genome methylation was reduced after knocking down DNMT1,and the whole genome methylation increased after knocking down TET1.After knocking down both DNMT1 and TET1,the result was between two single knockdowns.After knocking down DNMT1,some hypermethylated genes did not undergo methylation loss.Experimental studies have demonstrated that there is an reciprocal regulation relationship between DNMT1/3A/3B and TET1,and methylation is one of the pathogenic factors of lung cancer.The study of the effects of methylation and its elimination on cells may provide new treatment for lung cancer.However,specific gene methylation abnormalities lead to the occurrence of lung cancer,and further experimental verification is needed.
Keywords/Search Tags:DNMT1, TET1, epigenetics, lung cancer
PDF Full Text Request
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