MicroRNA-149 suppresses the proliferation and increases the sensitivity of ovarian cancer cells to cisplatin by targeting X-linked inhibitor of apoptosis

Abstract

Currently, ovarian cancer is identified as one of the leading causes of cancer-associated mortality in females. Despite numerous efforts that were made on developing novel treatments for ovarian cancer, the survival rate remains unsatisfactory. Considering the important regulatory role of miRNAs in different types of cancer, the present study aims to identify a novel therapeutic target for treatment of ovarian cancer. The expression of miR-149 was detected using reverse transcription-quantitative polymerase chain reaction in cancerous and normal cells. Furthermore, the effects of miR-149 on ovarian cancer cell activities were investigated using MTT assay, colony formation, flow cytometry and western blotting analysis. In the present study, it was revealed that microRNA (miR)-149 was significantly downregulated in ovarian cancer tissues and cell lines, and that the miR-149 expression was correlated with the patient prognosis. In addition, it was observed that forced expression of miR-149 increased the sensitivity of ovarian cancer cell to cisplatin. Based on bioinformatics analysis and luciferase assay, X-linked inhibitor of apoptosis (XIAP) was identified as a direct target gene of miR-149 in ovarian cancer cells. It was also demonstrated that XIAP expression was upregulated in the ovarian cancer tissues and cell lines, while it was negatively correlated with miR-149 in these tissues and cells. Furthermore, results revealed that ectopic expression of XIAP was able to abolish the miR-149-enhanced cell sensitivity to cisplatin. In conclusion, the present study revealed that miR-149 functioned as a tumor suppressor in the progression of ovarian cancer, increasing the sensitivity of ovarian cancer cells to cisplatin treatment.