Integrated analysis to find specific MicroRNAs and Genes Associated with Metastasis and Cisplatin and ۵-Fluorouracil Resistance in Gastric Cancer

Introduction: The main causes of cancer mortality can be metastasis and drug resistance. Genetic and epigenetic factors are the effective factors in drug resistance and metastasis. The goal of this project was to obtain microRNAs and genes that play a role in drug resistance and gastric cancer metastasis. Methods: The expression profile of genes was obtained using the GEO database. We examined protein-protein interaction and the signaling pathway analysis. The DEGs had differential expression between GC and normal tissues were selected by the GEPIA. We selected the regulating microRNAs by mirwalk. The expression of DEGs and miR between non-metastatic and metastatic tissues were measured. The cisplatin and ۵-Fu concentration by MTT and propidium iodide and Annexin V-FITC assay were choosen on sphere of MKN-۴۵. The cells were treated with drugs and compared the expression of DEGs and miRs by qRT- PCR. Results: CXCL۸, MMP۹, CCL۵, STAT۱, miR-۱۷-۵p, miR-۲۴-۳p, miR-۱۲۴-۳p, miR-۱۲۸ and miR-۱۴۵-۳p were selected which play important roles in drug resistance and metastasis. The expression levels of CXCL۸, STAT۱, miR-۱۷-۵p, miR-۲۴-۳p and miR-۱۲۴-۳p increased and miR-۱۴۵-۳p decreased significantly in metastatic tissues. Cells were treated with ۱ μg / ml cisplatin and ۱۰ μg/ml ۵-fu and were able to regrow. QRT-PCR results showed that the expression of miR-۱۷-۵p, miR-۲۴-۳p, miR-۱۲۴-۳p, CXCL۸, STAT۱ and MMP۹ were significantly increased. Conclusion: Up-regulation of miR-۱۷-۵p, miR-۲۴-۳p, miR-۱۲۴-۳p, CXCL۸ and STAT۱ involve in drug resistance. MiR-۱۴۵-۳p down-regulation induces metastasis and MMP۹ up-regulation in the treated group indicates that involves in resistance to cisplatin and ۵-Fu.