Mir-147 act as a tumor suppressor in ovarian cancer with targeting the ZEB1 and ZEB2 genes

Background: In women, ovarian cancer has an important role in mortality due to cancer. This malignancy is the eighth most common cancer among Iranian women. Surgery and chemotherapy are common treatments for cancers, including ovarian cancer. Most ovarian cancers are epithelial. The main problem with this type of malignancy is the difficulty in detecting it.Objective: In this study, we aimed to evaluate the expression of ZEB-1, ZEB-2, and Mir-147 in the ovarian cancer cell line before and after treatment with cisplatin as well as ovarian cancer tissues.Materials and Methods: In this study, 30 ovarian cancer specimens coupled their tumor marginal tissue were collected from Shahid Sadoughi Hospital. Sensitive (A2780S) and resistant (A2780CP) cell lines of ovarian cancer were grown in RPMI culture media. Then, cells were treated with different concentrations of cisplatin and cisplatin-IC50 was measured by MTT assay. RNA was extracted from treated cells and tissues and after cDNA synthesis, qRT-PCR was performed. Finally, the results were analyzed.Results: In 23 tumor samples, expression of Mir-147 showed a significant reduction in expression than controls (p=0.0001). The expression of ZEB-1and ZEB-2 genes expression in these tumor samples was significantly higher than controls (p<0.001). In the cisplatin-sensitive cell line, the expression of Mir-147 increased significantly after 24, 48 and 72 hr treatments (p<0.05). Also, a significant increase was observed in the resistant cell line after 72 hours of treatment with cisplatin. After 24, 48 and 72 hr cisplatin treatment, there was a significant decrease in expression of ZEB-1 and ZEB-2 genes in sensitive cell line. Moreover, 72 hr after treatment, there was a decrease in the expression of these genes in the resistant cell line.Conclusion: The results of this study showed a reduction in the expression of Mir-147 and an increase in the expression of the ZEB-1 and ZEB-2 genes in tumor tissue relative to its marginal control tissue. It also increased the expression of Mir-147 in the cell line after treatment with cisplatin and decreased expression of the ZEB-1 and ZEB-2 genes. Therefore, it can generally be concluded that in the tissue samples and ovarian cancer cell lines, the expression of Mir-147 as a tumor suppressor and ZEB-1 and ZEB-2 genes as an oncogene has been impaired.

Keywords:

Ovarian cancer , MIr-147 , Gene expression , Cisplatin treatment