Reprogramming Of H3K4 Histone Methylation In The Process Of Required Radioresistant Lung Cancer Cells

Lung cancer is one of the diseases leading to the death of human cancer today,the incidence of men in the first place and women occupy the second place.According to statistics,the number of deaths due to lung cancer each year has more than 1 million cases.According to pathological and clinical features,Lung cancer can be divided into non-small cell lung cancer(NSCLC)and small cell lung cancer(SCLC)two categories.NSCLC accounted for 80 to 90%.Most patients with NSCLC often lose their chances of surgery,mainly using radiotherapy-based combined therapy or radiotherapy alone,but the survival rate is only about 5%.The effect of radiation therapy on cancer cells is the sensitivity of cancer cells to ionizing radiation,but tumor cells are often resistant to ionizing radiation because of the mechanism of DNA damage repair,and thus limit the application of radiotherapy.The main indicator of epigenetic network is the covalent modification of chromatin,which can directly regulate the expression of genes and determine the important role of cell proliferation and differentiation,and it can work as a bridge between the internal and external environmental factors and genome genetic information.Histone methylation,acetylation and ubiquitination and other modifications can alter the transcriptional properties of DNA and the structure of chromatin.Methylation of histone lysine is catalyzed primarily by methyltransferase comprising the SET(Suppressor of Variegation,Enhancer of Zeste,and Trithorax)domain.Usually H3K4,H3K36,H3K79 methyl groups associated with chromatin structural activation and H3K9,H3K27 methyl groups associated with the silence region.It has been reported that the recruitment of DNA damage repair protein 53BP1 at the DSB site requires the acetylation of histone H4 and the methylation of H4K20.There are studies have shown that H2K36 methylation,which is dependent on Set2,can promote non-homologous terminal attachment(NHEJ)in fission yeast,and that H3K36 acetylation,which relies on Gcn5,promotes homologous recombination repair(HR).In 2010,it has been reported tht H3K4me3 catalyzed by Setlp plays an important role in DNA DSB repair in yeast cells,and Setlp is dependent on RSC complexes.H3K4me3,a positive histone modification regulated by menin and MLL,which,in addition to regulating the activity of some gene promoters to promote gene transcription,can also alter the conformation of chromatin and make it more loose.So does this histone modification mechanism and its methyltransferase TrxG complex also participate in the radiation damage induced by ionizing radiation in lung cancer cells,and then participate in the radiation resistance of lung cancer cells.In this study,two radiation resistant models were established using two lung adenocarcinoma cells A549(K-Ras G12S mutant)and H1299(P53 null).By means of molecular biology analysis,it was found that the epigenetic mechanisms of radiation resistance of lung cancer cells with different genetic backgrounds were different,and in A549 cells,the methyl transferase of H3K4me3 and the MLL of TrxG complex were produced in radiation resistance And then decreased to demonstrate that MLL was involved in the production of radiation resistance and that H3K4me3 was activated at the transcription initiation site.Thus,this study provides a new idea for the epigenetic mechanisms of radiation resistance of lung cancer cells.This will provide a new molecular marker for the rational development of lung cancer radiotherapy program,and provide interesting ideas for the study of radiotherapy sensitizer in lung cancer.