Background Cisplatin-resistant gastric cancer (GC) occurs in patients with GC treated with cisplatin-based chemotherapy, which results in disease progression and early recurrence during the treatment. cells, and arrested the cells at G2/M phase. Gene ontology analysis revealed that this DEGs mainly regulate metabolic process, immune system, locomotion, cell adhesion, cell growth, cell death, cytoskeleton business, cell binding, transmission transducing activity, and antioxidant activity. Kyoto Encyclopedia of Genes and Genomes analysis showed that this DEGs were mainly involved in the PI3K-Akt signaling pathway, Rap1 signaling pathway, proteoglycans in malignancy, regulation of actin cytoskeleton, and pathways in malignancy. Concluisons The present study is the first to interrogate mRNAs profiles in human GC cells with cisplatin resistance using RNA sequencing, which may assist in discovering potential therapeutic targets for cisplatin-resistant GC patients. value [FDR q value] 0.001 and cut-off of |Log2Ratio|1. GO (Gene Ontology) analysis and Kyoto Encyclopedia of Genes and Genomes database (KEGG) pathway analysis GO analysis was carried out to elucidate the biological functions of the DEGs in the experiment. We downloaded the GO annotations from Gene Ontology (values. Pathway analysis was utilized to find out the significant pathways of the DEGs according to KEGG. Fishers exact test was used to select the significant pathways, and the threshold of significance was defined FDR. Quantitative real-time PCR analysis (qRT-PCR) Total RNA was extracted as mentioned above and reversely transcribed into cDNA using the PrimeScript RT Grasp Mix (TaKaRa, Dalian, China). The expression of target genes randomly selected from the top 20 dysregulated DEGs that were independently validated using the SYBR Green I PCR Kit (Takara) following the manufacturers standard protocols. Fold switch (2?Ct) was normalized to GAPDH . The primer sequences are shown in Table Ptgs1 1. Table 1 Primers used in quantitative real-time PCR analysis. test and one-way ANOVA. Linear regression was performed with Pearsons correlation coefficient GSK343 inhibitor (R). Differences were considered significant when and spheroid colony formation em in vitro /em ) cells of these 3 GC cell lines are more resistant to cisplatin than CD44? cells [28,29]. We observed that with the acquisition of cisplatin resistance, SGC7901 cells transitioned from epithelial state to mesenchymal state, the expression of the epithelial GSK343 inhibitor maker E-cadherin was downregulated, and the expression of mesenchymal makers N-cadherin and Vimentin were significantly increased. At the same time, the bioinformatics analysis of the differentially-expressed genes showed that many genes were enriched in GSK343 inhibitor molecular mechanisms (using GO analysis), such as cell localization, locomotion, biological adhesion (biological process), cytoskeleton business (cellular component), cell binding (molecular function), and pathways (using KEGG pathway analysis), such as cell adhesion molecules, ECM-receptor conversation, focal adhesion, PI3K-Akt signaling pathway, and Hippo signaling pathway, which, as mentioned above, are significantly correlated with EMT and CSCs properties [27,30,31]. These results show a strong GSK343 inhibitor mechanistic link of EMT, CSCs, and cisplatin resistance in SGC7901 cells. Additionally, some of the bioinformatic results have been confirmed to be involved in cisplatin resistance in other cancers. For example, in the Rap1 signaling pathway, Lu Xiao and colleagues discovered that the cytoplasmic Rap1-NF-B-BCL2 axis is usually a key mechanism in cisplatin resistance in non-small cell lung malignancy . Studies exhibited that cisplatin-induced oxidative stress is one of the molecular mechanisms of cisplatin pharmacology , and our bioinformatic results showed that antioxidant activity might play a role during the acquisition of cisplatin resistance. There may be many underlying mechanisms that give rise to cisplatin resistance, because some of the GO and KEGG terms proposed in our study, such as metabolic process, immune system, and estrogen signaling pathway, are rarely reported. Conclusions Taken together, the present study provides a global horizon of the function of the DEGs between SGC7901/DDP and SGC7901/S cells, and explores the potential mechanisms that induce cisplatin resistance. Although the past years.