epidrug modulated expression of mir‌-152 and mir-148a reverse cisplatin resistance in ovarian cancer cells: an experimental in-vitro study

Cisplatin is a common agent which is used to treat epithelial ovarian cancer (eoc), but cisplatin resistance is a major obstacle in successful treatment of ovarian cancer. aberration in epigenetic changes play an important role in disregulation of gene expression. mir-152 and mir-148a are frequently down-regulated in eoc due to promoter hyper-methylation. dna methyltransferase1 (dnmt1), the main enzyme in maintenance of the pattern of dna methylation, is one of the targets of mir-152 and mir-148a. aberrantly up-regulation of dnmt1 is responsible for silencing of tumor suppressor genes in carcinogenesis. we hypothesized that re-expression of mir-152 and mir-148a and consequently down-regulation of dnmt1 may resensitize cancerous cells to chemotherapeutics agents. the aim of the present study is to investigate the effect of 5-azacytidine (5-aza) and trichostatin a on mir-152 and mir-148a expression in a2780cp ovarian cancer cell line. optimal doses of 5-azacitidine and tsa were measured by 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (mtt) assay. a2780cp cell line was treated by each drugs, alone or in combination and the expression of mir- 148a, mir-152 and dnmt1 was evaluated by real-time quantitative reverse transcription- polymerase chain reaction (rt-qpcr). the results revealed that tsa and 5-azacytidine are able to revive the expression of mir-148a and mir-152 genes and mediate growth inhibition of epithelial ovarian cancer cells. the present study suggests that re-expression of mir-148a and mir-152 by epigenetic therapy aiming to dnmt1 suppression might resensitize resistant ovarian tumors to conventional chemotherapy.