Investigation of epidrugs effect on microrna148a expression pattern in a2780cp epithelial ovarian cancer cell line

Epithelial Ovarian Cancer is the most lethal malignancy among of female reproductive system. Whereas cisplatin is currently a frontline chemotherapeutic agent for ovarian cancer, chemoresistanceremains a major barrier to successful therapy. MicroRNAs are small non-coding RNAs that are aberrantly expressed in various carcinomas including ovarian cancer. MicroRNA-148a was reported tobe downregulated by promoter hypermethylation in ovarian cancer. Various studies have identified numerous miRNAs and their diverse targets. DNMT1 is one of the most important targets of miR- 148a. Overexpression of DNMT1 is responsible for silencing of tumor suppressor genes and those involved in response to chemotherapy. Therefore, factors that can reverse cisplatin resistance results in increasing long-term survival rates of EOC patients. In this study, we evaluated the effect of Trichostatin A and 5-azacitidine on the expression of mir-148a and its target DNMT1. The effect of Trichostatin A and 5-azacytidine was evaluated on A2780CP cell line. We measured optimal doses by MTT assay, expression of miR-148a and by qRT-PCR when exposed to these drugs alone or in combination. Our results suggest Trichostatin A and 5-Azacytidine separately and in combination, can revive the expression of miR-148a gene while, DNMT1, the target of miR-148a, was consequently suppressed. We proposed that the expression of miR-148a could be regulated by both histone deacetylation and promoter hypermethylation in A2780CP cell line. It is expected that the use of 5- Azacytidine and Trichostatin A that cause upregulation in miR-148a expression and consequently DNMT1 suppression, can resensitize A2780CP cells to cisplatin

Keywords:

Ovarian Cancer , Gene and Cancer , Cancer Genetics , Cancer Treatment and Management , Drugs and Cancer , Chemotherapy