Bioinformatics Analysis Of Differential MiRNA Expression In Cisplatin-sensitive And Resistant Lung Adenocarcinoma

Background:lung cancer has the highest morbidity and mortality in China.In recent years,Lung adenocarcinoma(Lung adenocarcinoma,LUAD)the incidence of more than Lung squamous carcinoma,become the main pathological types of Lung cancer,in recent years,continuously put forward new cancer treatments,but in the non-surgical treatment of Lung cancer,the application of cisplatin is still extensive,earlier in platinum antitumor medicine belongs to the research and development and clinical application of more mature a drug.However,chemotherapy is often the major obstacle to multidisciplinary treatment of lung cancer due to the limitations of intrinsic and acquired drug resistance.Therefore,finding a solution to cisplatin resistance in tumors has become a hot topic for clinical researchers.In recent years,the miRNA cisplatin resistance mediated tumor has become the research focus in the research,numerous studies have demonstrated that the development of tumor miRNAs play an important role,the polymorphism of miRNAs and abnormal expression can lead to cancer drug resistance related pathways of gene expression levels and tumor cell cycle changes,to break the balance,and then change the sensitivity of tumor cells to cisplatin.However,the role and mechanism of specific miRNAs in non-small cell lung cancer(NSCLC),especially in chemotherapy drug resistance in lung adenocarcinoma,remain unclear.Based on this,we screened differentially expressed miRNAs by using conventional miRNA technology and combined with the microarray information of miRNAs in lung adenocarcinoma sensitive/resistant cell lines and tissue samples with complete GEO data set.Through a series of bioinformatics analysis and evaluation,we proposed a hypothesis for the mechanism of cisplatin resistance at the molecular level.And provides the foundation for the subsequent series of horizontal experimental verification.It is expected to be a new discovery in reversing cisplatin resistance in lung cancer.Objective:to explore the differential expression,potential targets and biological functions of related special miRNAs in sensitive and drug-resistant lung adenocarcinoma with miRNA as the starting point.It provides theoretical support and guidance for the study of cisplatin resistance mechanism in lung cancer.Methods:1.Using the GEO data set to download the data set of lung adenocarcinoma cisplatin sensitive/resistant different cell lines GEO_Cell line and tissue samples GEO_Tissue data information,the retrieval results were analyzed by computer and manually,and the related drug resistance vs.drug sensitivity differentially expressed miRNAs set was screened and sorted out.And the use of statistical tools to further collate miRNAs that were differentially expressed in both cell lines and tissue samples were detected.2.Prediction of miRNA target genes,enrichment analysis of significant function and signal pathway,construction of mirna-significant function--network diagram and signal pathway diagram.3.Construct the regulatory network of miRNA and genes,and determine the core regulated miRNA and its target genes.4.MTT assay was used to verify the drug-resistant lung cancer cell line IC50.Rt-qpcr assay verified the above differential mirnas.Results:1.Through the analysis of differentially expressed mirnas in the database,there were 7mirnas with changes in cell lines and lung cancer tissues(hsa-mir-193b-3p,hsa-mir-21-3p,hsa-mir-26a-5p,hsa-mir-27b-3p,hsa-mir-29c-3p,hsa-mir-767-5p,and hsa-mir-29a-3p).Among them,hsa-mir-193b-3p was upregulated in both cell lines and lung cancer tissues,while the rest showed opposite expression in tissues and cell lines.2.Target gene prediction and pathway,GO and other bioinformatics analysis were carried out for the above differentially expressed miRNAs to seek for its significant functional changes and signal pathway enrichment prediction,showing its influence onspecific biological processes.3.Conduct preliminary horizontal verification on the above experimental results,and the results are basically consistent with the database.Conclusion:1.There were 7 simultaneously regulated mirnas in lung adenocarcinoma cell lines/tissues,but only hsa-mir-193b-3p was in the same regulated state.2.Differential mirnas,mainly composed of hsa-mir-193b-3p,mainly regulate three target genes,MMP14,LAMC1 and OSMR,and participate in a total of 14 signal transduction pathways,most notably the pi3k-akt signaling pathway,MAPK signaling pathway and mTOR signaling pathway.3.It was inferred that differential mirnas such as hsa-mir-193b-3p were involved in the biological processes of cell survival,proliferation and differentiation through the above signaling pathways,leading to cisplatin resistance in lung adenocarcinoma.