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Effects Of Valproic Acid On H19 Expression And Methylation Pattern In A549 Cells

Posted on:2019-08-29Degree:MasterType:Thesis
Country:ChinaCandidate:Y HaoFull Text:PDF
GTID:2404330542986663Subject:Zoology
Abstract/Summary:PDF Full Text Request
The gene H19 is located on the 11 th human chromosome,on the 7th chromosome of the mouse,the parental blot,maternal expression,and its expression is controlled by epigenetics(DNA methylation and histone acetylation).Gene H19 as an imprinted gene plays an important role in the early embryonic development and cell physiological activities of organisms,including cell cycle,apoptosis,cell growth and differentiation.The study found that Lnc RNA H19,as an oncogene,plays an important role in the development of cancer.Lnc RNA H19 is abnormally expressed in bladder,breast,colon,and brain cancers.In addition,the expression level of Lnc RNA H19 is considered as a potential biomarker in cancer patients.The purpose of this experiment was to explore how to regulate the expression pattern of Lnc RNA H19 in human lung cancer cell line A549.The experimental project includes two parts,exploring the effects of histone deacetylase inhibitor valporic acid(VPA)on Lnc RNA H19 expression and DNA methylation patterns in A549.In this study,Lnc RNA H19 was found to be abnormally expressed in A549 lung cells.In addition,compared with the hemimethylation status of the differentially methylated region(DMR)in human 293 cells,gene H19 showed an abnormal demethylation state.After treatment of A549 cells with small molecule drug VPA,real-time fluorescence quantitative PCR was used to detect VPA.The results showed that VPA could inhibit the expression of Lnc RNA H19 in A549 cells,but it could not change the hypomethylation status of gene H19 DMR.This study further explored the relationship between Lnc RNA H19 expression and key epigenetics enzymes,methyltransferase DNMTs and histone deacetylase HDACs.The experimental results showed that the expression of HDAC1 and DNMT1 was increased in VPA-treated A549 cells.In addition,the study design explored the apoptosis and cell cycle conditions after VPA treatment.The experimental results show that VPA can promote A549 cell apoptosis and change A549 cell cycle progression in A549 cells.At the same time,this study found that VPA can promote the expression of P53 apoptotic protein in A549 cells.The data showed that the expression of Lnc RNA H19 plays an important role in cancer.VPA may induce the activation of P53 protein by inhibiting the expression of gene H19 in A549 cells,thus promoting apoptosis.Taken together,the results of this study indicate that VPA inhibits the expression of Lnc RNA H19 by regulating HDAC1 and DNMT1,and the decreased expression of Lnc RNA H19 can promote A549 cell apoptosis and change the cell cycle.The research results provide potential target sites for drug research of lung cancer,and also provide a theoretical basis for further analysis of the role of gene H19 in cancer.
Keywords/Search Tags:apparent genetics, valproic acid(VPA), Gene H19, A549, Cell apoptosis
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