Integrated analysis to find MicroRNAs and Genes Associated with Metastasis and Cisplatin and 5-Fluorouracil Resistance Gastric Cancer

Background Metastasis and drug resistance are the leading causes of cancer-related mortality worldwide. Studies suggest that epigenetic factors play a crucial role in these common complications. Objective This study aimed to identify key regulators of drug resistance and metastasis in gastric cancer by utilizing a combined in silico and in vitro approach. The goal was to uncover genes and microRNAs that could serve as determining factors and patterns in chemoresistance to common chemotherapy drugs and metastasis. Materials and Method The expression profile of genes that differed between drug resistance and sensitive gastric cancer patients was obtained from the GEO database. Then protein-protein interactions were provided using Cytoscape software. The selected genes were assessed for differences in gastric cancer and normal tissues using the Gepia website. Then, the MiRWalk database searched to find regulating microRNAs. MKN-45 cells were treated with Cisplatin (CCDP) and 5-Fluorouracil (5-FU) two times. Finally, the evaluation of selected genes and micro-RNAs in non-metastatic and metastatic tissues and 5-FU/CCDP resistance MKN-45. Results Data revealed 28 genes differentially expressed between drug-resistant and drug-sensitive gastric cancer, exhibiting differences in both normal and tumor tissues. Protein interaction analysis highlighted CXCL8, MMP9, CCL5, and STAT1; as crucial genes influencing both metastasis and drug resistance in gastric cancer patients. Moreover, miR-17-5p, miR-24-3p, miR-124-3p, miR-128, and miR-145-3p were introduced here which play important roles in regulating both processes. The expression levels of CXCL8, STAT1 , miR-17-5p, miR-24-3p, miR-124-3p increased, and miR-145-3p decreased significantly in metastatic tissues and 5-FU/CCDP resistant MKN45 than non-metastatic and sensitive ones. Conclusion Up-regulation of miR-17-5p, miR-24-3p, miR-124-3p, CXCL8 , CCL5 , MMP9 , and STAT1 is implicated in metastasis and drug resistance to both cisplatin and 5-FU. Also, down-regulation of miR-145-3p induces metastasis and drug resistance possibly via STAT1 and MMP9 .