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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.

Human mesenchymal stem cells (hMSCs) have remarkable potential for use in regenerative medicine. However, one of the great challenges is preserving their potency for long time. This study investigated the effect of miRNA ectopic expression on their proliferation and also on the expression level of Parp1 as an epigenetic switch preserving pluripotency in hMSCs. A cationic liposome was prepared as an efficient carrier for miRNA delivery. The miRNA loading efficiency and physical stability of vesicles were measured, and their scanning electron microscopic shapes determined. hMSCs were transfected with miR-302a and miR-34a followed by assessment of their proliferation potency with MTT assay and measurement of the expression of Parp1 by quantitative polymerase chain reaction (QPCR). Cell transfection with miR-302a and miR-34a efficiently and differentially affects the proliferation potency of hMSCs and the expression level of Parp1 as the key epigenetic factor involved in pluripotency. While miR-302a increases Parp1 expression, miR-34a suppresses it significantly, showing differential effects. Our results demonstrated that miRNA-based treatments represent efficient therapeutic systems and hold a great promise for future use in regenerative medicine through modification of hMSC pluripotency and epigenome., EXCLI Journal;Vol. 17 2018