Exploring miRNA profile associated with cisplatin resistance in ovarian cancer cells

Abstract

Ovarian cancer is a common and lethal malignancy among women, whereas chemoresistance is one of the major challenges to its treatment and prognosis. Chemoresistance is a multifactorial phenomenon, involving various mechanisms that collectively modify the cell's response to treatment. Among the changes that arise in cells after acquiring chemoresistance is miRNA dysregulation. Here, this study aimed to identify miRNAs expression changes related to cisplatin resistance in ovarian cancer cells. The miRNA expression profiles of a cisplatin-sensitive A2780 cell line and two cisplatin-resistant cell lines, A2780cis and SK-OV-3, were analyzed using PCR array and qPCR. Accordingly, the miRNAs that were differentially expressed were further investigated to identify their biological functions and the target pathways using Gene Ontology (GO) annotation and KEGG pathway analyses. In order to evaluate the clinical significance of the differentially expressed miRNAs, survival analysis was carried out using expression data for ovarian cancer patients available in the Kaplan-Meier (KM) plotter database. The current work demonstrates that Nine miRNAs were found to be upregulated in cells resistant to cisplatin. Clearly, these miRNAs have functions in cell death/survival related processes and treatment response. They may also target pathways involved in treatment response like PI3K-Akt, pathway in cancer and MAPK. Interestingly, High expression of hsa-miR-133b, hsa-miR-512-are, hsa-miR-200b-3p, and hsa-miR-451a is related to poor overall survival in patients diagnosed with ovarian cancer. Our findings suggest that hsa-miR-133b, hsa-miR-512-5p, hsa-miR-200b-3p, and hsa-miR-451a are good candidates for future studies aimed to establishing functional links and exploring therapeutic interventions to overcome cisplatin resistance.

Keywords

• Cisplatin
• Ovarian cancer
• miRNA
• Chemoresistance
• Gene ontology
• Pathway analysis