The Role And Mechanism Of Suv420H2 In The Development Of Lung Adenocarcinoma

As one of the members of histone lysine methyltransferase,color spot 4-20 homolog 1 inhibitor 2(Suv420H2)is composed of three parts:N-terminal domain,set domain and Zn post set domain.Suv420H2 regulates a variety of physiological functions by trimethylation in histone 4-lysine 20(H4K20),including the maintenance of transcription and genome integrity,fat metabolism,cell aging and osteoblast differentiation.In addition,histone lysine methyltransferase Setd8 and Suv420H1 can also be used to modify H4K20 with monomethylation and demethylation.Previous studies have shown that the trimethylation of Suv420H2 is related to the occurrence and development of cancer,and the absence of Suv420H2 has been considered as a marker of human cancer.In breast cancer,the lack of Suv420H2 accelerates the development of metastatic breast cancer,moreover,recent studies have found that the high expression of Suv420H2 in pancreatic cancer is conducive to the transformation of pancreatic cancer cells to mesenchymal cells,and the increase ability of cell invasion.At present,there are few reports on the research of Suv420H2 in cancer,and there is no report on the research of Suv420H2 in lung cancer.In this study,the role of Suv420H2 in human lung adenocarcinoma was systematically studied,and the mechanism of Suv40H2 in the migration of human lung adenocarcinoma was preliminarily discussed.In this study,the expression of histone methyltransferase(HMT)in lung adenocarcinoma cell lines BEAS-2B,A549,NCl-H1395,NCl-H1373,NCl-H1573 and NCl-H1299 cells was detected by Real-time PCR.Finally,the stable and low expression gene Suv420H2 in lung adenocarcinoma cell lines was selected as the research object.We further detected the expression level of Suv420H2 in lung adenocarcinoma cell line at protein level,which were consistent with the results of Realtime PCR.All the results demonstrated that Suv420H2 was low expression in lung adenocarcinoma cell line.In order to study the role of Suv420H2 in the carcinogenesis and development of lung adenocarcinoma,the overexpression plasmid Suv420H2 was constructed and stably overexpressed in A549 cells with low expression of Suv420H2.The effect of Suv420H2 overexpression on cell proliferation and migration was detected in vitro.Wound healing test and Transwell test showed that overexpression of Suv420H2 promoted the proliferation of A549 cells.CCK8 and plate cloning experiments showed that Suv420H2 overexpression had no effect on the proliferation of A549 cells.In order to further study the mechanism of Suv420H2 promoting the migration of A549 cells,we detected the phosphorylation of Akt,p38,ERK,p65 and the protein expression of migration related molecules in the Akt,MAPK,ERK and NF-kB signaling pathways at the protein level The expression of E-cadherin was up-regulated by inhibiting the phosphorylation of p65 and TAK1,and the cell migration was promoted by overexpression of Suv420H2In order to further study the up-regulation of p38 phosphorylation induced by overexpression of Suv420H2,we found that p38 interacted with Suv420H2 by IP assay.Pull down test showed that Suv420H2 and p3 8 only existed in the consent complex,and no direct interaction occurred.Then we detected the relationship between p38 upstream kinase and Suv420H2 by IP experiment.The results showed that Suv420H2 interacted with MKK3,which promoted the activation of p38 by MKK3.In conclusion,Suv420H2 promotes the migration of lung adenocarcinoma cell line A549.The mechanism was involved with up regulation,of the phosphorylation of p38 and N-cadherin in A549 cell line with Suv420H2 overexpressed,moreover,the activation of p38 was promoted with MKK3,both of the results promotes the cell migration ability.The purpose of this study is to clarify the function and molecular mechanism of Suv420H2 in lung adenocarcinoma metastasis,hoping to provide a new theoretical basis for the treatment of lung adenocarcinoma metastasis.