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Identification of new biomarkers for cisplatin-resistance in A549 human lung adenocarcinoma cells by an integrated bioinformatical analysis

	author = {Dong Wang and Leina Ma and Qingxia Ma and Jia Liu and Guohui Jiang},
	title = {Identification of new biomarkers for cisplatin-resistance in A549 human lung adenocarcinoma cells by an integrated bioinformatical analysis},
	journal = {Translational Cancer Research},
	volume = {6},
	number = {3},
	year = {2017},
	keywords = {},
	abstract = {Background: Drug resistance plays an important role in the failure of clinical therapy. This study aimed to identify the key genes related to cisplatin resistance in A549 human lung adenocarcinoma cells. 
Methods: The mRNA microarray dataset E-MEXP-3123 and miRNA dataset GSE43249 were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) and miRNAs (DEMs) between parental and cisplatin-resistance A549 lung cancer cells were identified. Functional enrichment analysis and pathway analysis were performed by using the DAVID database. Protein-protein interactions of DEGs, microRNAs (miRNAs) network and their potential gene targets were formed by Cytoscape. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to validate the identified candidate genes in cisplatin-resistant A549 cells. 
Results: Firstly, a total of 499 DEGs were identified from E-MEXP-3123. In gene ontology (GO) term analysis, DEGs were significantly involved in signal transduction, oxidation-reduction process, multicellular organism development, cell adhesion and inflammatory response. Pathway analysis showed that the most significant pathways were neuroactive ligand-receptor interaction, endocytosis and hippo signaling pathway. PPI network showed that the top five hub genes were CDH1 (cadherin 1), BDKRB2 (bradykinin receptor B2), FPR2 (formyl peptide receptor 2), CCR5 (C-C chemokine receptor type 5) and YWHAE (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon). Secondly, 12 DEMs were identified from GSE43249, and the top six DEMs were miR-194, miR-192, miR-574-3p, miR-106b, miR-146a and miR-182. In subsequent qRT-PCR experiments, low expression levels of miR-192, miR-106b, miR-182 and high expression level of miR-574-3p were confirmed in cisplatin-resistant group compared with control group. Meanwhile as predicted, the overexpression of NCALD, SPIN1 that are miR-182 potential targets and the weak expression of PSMA4 that is miR-574-3p potential target were also experimentally validated in cisplatin-resistant lung cancer cells. 
Conclusions: These key genes identified in our study might provide new clues for developing effective strategies against cisplatin resistance during lung adenocarcinoma treatment.},
	issn = {2219-6803},	url = {}