MicroRNA-519a inhibits the proliferation and promotes the apoptosis of ovarian cancer cells through targeting signal transducer and activator of transcription 3
نویسندگان
چکیده
Ovarian cancer is a highly prevalent cancer among women. Recent studies have indicated that microRNAs (miRs) may serve important roles in the pathogenesis of ovarian cancer. miR-519a was observed to be downregulated in tissue samples of patients with ovarian cancer; however, its role in ovarian cancer requires further investigation. The aim of the present study was to examine the role of miR-519a in the pathogenesis of ovarian cancer and determine its direct target. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to examine the expression of miR-519a in 20 patients ovarian cancer and 20 normal ovarian tissue samples. Subsequently, SKOV3 cells were cultured and transfected with miR-519a mimics, while MTT and Annexin V assays were performed to investigate the role of miR-519a in the proliferation and apoptosis of SKOV3 cells. In addition, RT-qPCR and western blotting were used to determine the expression levels of miR-519a, signal transducer and activator of transcription 3 (STAT3), myeloid cell leukemia 1 (Mcl-1) and B-cell lymphoma-extra large (Bcl-xl) in untransfected and miR-519a mimic-transfected SKOV3 cells. Dual-luciferase reporter assay was also performed to confirm whether STAT3 was a direct target of miR-519a. The results revealed that miR-519a was significantly downregulated in tissue samples of patients with ovarian cancer as compared with the normal ovarian tissues. Furthermore, transient overexpression of miR-519a inhibited the proliferation and promoted the apoptosis of SKOV3 cells, as well as decreased the mRNA and protein expression levels of STAT3, Mcl-1 and Bcl-xl. Finally, dual-luciferase reporter assay confirmed that STAT3 was a direct target of miR-519a. In conclusion, the present study proved for the first time that miR-519a functions as a tumor suppressor by targeting STAT3 in ovarian cancer, suggesting that miR-519a may be a potential biomarker for the diagnosis and treatment of ovarian cancer.
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