The Research Of Interaction Protein Of PRMT7 And Its Contribution To The Metestis Of NSCLC

Lung cancer is the most lethality malignant tumor in the world.Pathological classification of lung cancer can be divided into small cell lung cancer,squamous cell carcinoma,adenocarcinoma and large cell carcinoma.Squamous cell carcinoma,adenocarcinoma and large cell carcinoma are also called non-small cell lung cancer(non-small cell lung cancer),which accounts for about 85% of the total lung cancer(NSCLC).In recent years,with the development of biomedicine,the diagnosis and treatment of lung cancer have made great achievements.In addition to traditional tumor therapies such as surgery,radiotherapy and chemotherapy,some targeted inhibitors of EGFR and ALK genes such as gefitinib,erlotinib,icotinib were also used for cancer treatment,which can bind target gene and inhibit its activity specifically and inhibit the proliferation and growth of tumor.The use of targeted drugs had greatly improved the survival of lung cancer patients.In the clinic,most lung cancer patients are advanced when diagnosed.For these advanced lung cancer patients,whose lung cancer cells have been transferred and diffused.Drug treatments have little effects to inhibit tumor invasion.Therefore,the survival of patients with advanced lung cancer is very low.In order to improve the survival rate and life quality of lung cancer patients,researchers have focused on lung cancer metastasis and lung cancer cell invasion as the focus of treatment of lung cancer.Researchers have discovered that epigenetic modification of tumor cells,genes,and proteins plays an important role in the metastasis of cancer cells.Previous studies also shown that PRMT7 can induce epithelial mesenchymal transition(EMT)in breast cancer,and enhance the invasive ability of breast cancer cells.Previous results in this study also showed that PRMT7 was highly expressed in highly metastatic lung cancer cells and lower in low metastatic lung cancer cells.Therefore,PRMT7 may be involved and played a critical role in the metastasis of lung cancer.In this study,the effects of PRMT7 on the growth,proliferation and invasion of lung cancer cells were investigated,then the PRMT7 integrating proteins and their physiological metabolism pathway genes and participation were clarified by immunoprecipitation(Chromatin Immunoprecipitation COIP)connected with bioinformatics analysis of binding protein mass spectrometry in lung cancer cells.Finally,with the RNA interference of candidate genes,the expression of candidate genes on the expression of PRMT7 and the invasion of lung cancer cells were investigated.The results showed that:(1)the expression of PRMT7 in 95D cells was higher which was lower in 95Ccells;(2)In lung cancer cells A549 and SPC-A-1 cells,over expressed PRMT7 enhanced the ability of cell invasion;(3)The cell growth was not affected by the expression of PRMT7 through CCK8 excrement;(4)Cell cloning experiment show that the cell proliferation was not affected by the expression of PRMT7 in lung cancer cells;(5)The PRMT7 interacting protein genes,respectively PKM2,HSPA5,EEF2,DLAT,XRCC6,GPI and G6 PD were clarified after the experiment of co-immunoprecipitation with PRMT7 in lung cancer cell,(6)After the database searching and selection,5 genes,which named PKM2,HSPA5,EEF2,DLAT,XRCC6,were finally selected for further analysis which were involved in tumor cell glycolysis,protein folding,protein translation and double strand DNA damage repair respectively;(7)RNA interference of PRMT7 in A549 and SPC-A-1 showed that the cell invasion ability of lung cancer was inhibited when the EEF2 and HSPA5 were interfered;(8)In A549 cells.Expressions of PRMT7 were decreased when EEF2 and HSPA5 were interfered;In SPC-A-1 lung cancer cells,the expression of PRMT7 were also decreased when HSPA5 was interfered,which had no significant difference when EEF2 was interfered.Therefore,both EEF2 and HSPA5 can inhibit the expression of PRMT7 in A549 cells.But in SPC-A-1 cells,the expressions of PRMT7 were inhibited by HSPA5,and contrary,cannot effect by EEF2.In conclusion,the results of this study showed that the expression of PRMT7 and cell invasion can be effectively inhibited by the PRMT7 interaction protein HSPA5 in A549 and SPC-A-1cells.Therefore,HSPA5 can be used as an effective target for targeted drugs,and that drugs can effectively inhibit the activity of HSPA5 would inhibit lung cancer cell invasion.EFF2 cannot influence the expression of PRMT7 in SPC-A-1 cells,but has a critical effect on cell invasion.Therefore,the mechanism of its impact on cell invasion remains to be further studied.In addition,other candidate genes which were associated with cell invasion will be talked about in further studies.