Repression Of Dicer Is Required To Maintain Invasive Phenotype And Chemo-resistance In Ovarian Cancer

Objective:Dicer is a key enzyme that processes miRNA precursors into their mature form, enabling them to regulate gene expression. However, the effects of Dicer on biological behavior of cancer cells remain largely unclear. This work is aimed to study the role of Dicer in biological behavior and chemosensitivity of ovarian cancer and its regulation by histone methyltransferase EZH2.Methods:Dicer was knocked down by siRNA. Expression of Dicer mRNA and protain were measured by qPCR and Western blot analysis, respectively. Cell viability was evaluated in vitro by MTT proliferation assays. Cell proliferation was detected by BrdU incorporation assay. Cell migration capability was examined by Transwell migration assay. Cell cycle was analyzed by propidium iodide flow cytometry assay, Assessment of chemo-resistance to cisplatin was determined by the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. After the stable EZH2-knockdown A2780 cells was obtained. Expression of Dicer mRNA and protain were measured by qPCR and Western blot analysis, respectivly.Results:Dicer down-regulation promoted cell proliferation, migration and cell cycle progression in ovarian cancer cell A2780 and SKOV3. Furthermore, Dicer expression was significantly decreased in cisplatin-resistant A2780 cells (A2780/DDP) compared with parental A2780. Knockdown of Dicer by RNA interference decreased the sensitivity of A2780 cell to cisplatin. Moreover, EZH2 depletion by shRNA increased the expression of Dicer in vitro.Conclusions:Dicer plays a critical role in numerous biological/pathological processes of ovarian cancer.