Bioinformatic analysis of miRNA-mRNA interactions and related biological pathways in platinum-resistant epithelial ovarian cancer cells

چکیده مقاله

Introduction: Epithelial ovarian cancer (EOC) is one of the most lethal gynecologic cancers. Chemoresistance of tumor cells and disease relapse often result in treatment failure and death of patients. Since better understanding the molecular mechanism of chemoresistancy could led to increasing the efficiency of treatment methods, in this study we aimed to evaluate the molecular pathways that regulate chemoresistancy. Methods: miRNA profiling dataset was retrieved from the NCBI Gene Expression Omnibus (GEO) database by accession number GSE93794. This dataset demonstrated 3 Epithelial Ovarian Cancer cell lines Platinum-resistant vs. their parental. Initial bioinformatics analyses were performed using GEO2R. Top 5 up-regulated miRNAs were assessed by miRwalk web-tool to find their target mRNAs. Moreover related pathways and biological processes were explored using enrichr bioinformatics tool. Results: Our result showed that miR-365a-3p, miR-299-3p, miR-24-1-5p, miR-361-5p and miR-29b-1-5p are 5 top up-regulated miRNAs. Moreover studying the mRNA targets such as FAM166B, FAM214B, TESK1, ARHGEF39 and so on indicated that these microRNAs mostly involved in cell-cell communication, cell-extracellular communication, extracellular remodeling, cell mobility and metastasis related processes that are followed by chemoresistance and tumor relapse. Discussion: These findings specified that in concordance with previous reports metastasis related processes could be correlated to different responses to platinum in ovarian cancer cells. So molecular targeting of these biological processes could be effective in better outcome of ovarian cancer therapy.