The Clinical Significance And Functional Research Of MicroRNA-145 In Epithelial Ovarian Cancer

ObjectiveThe expression levels of miR-145 in cancerous tissues from patients with epithelial ovarian cancer as well as ovarian cancer cell lines were detected.The expression difference of miR-145 between serums of epithelial ovarian cancer patients and those of healthy controls was compared.Moreover,the association of serum miR-145 with patients' clinicopathological features and survival was analysed.Finally,the function of miR-145 in the carcinogensis of ovarian cancer were determined using in vitro experiments and in vivo xenograft tumor model experiment.MethodsReverse transcription-quantitative polymerase chain reaction(RT-qPCR)was used to determine the expression of miR-145 in 45 cases of epithelial ovarian cancer tissues,8 cases of normal epithelial ovarian tissues,as well as normal ovarian epithelial cell line(IOSE-386)and 4 different ovarian cancer cell lines(A2780,OVCAR-3,SKOV-3 & HO8910).The expression of miR-145 was also detected in 45 cases of serums from epithelial ovarian cancer patients and 45 cases of serums from healthy controls.The relationship between the miR-145 expression level and patients' clinicopathological indicators was analyzed by the Chi-Square analysis.Kaplan-Meier survival analysis was used to investigate the association of miR-145 expression level with patients' survival.The function of miR-145 in the carcinogenesis of epithelial ovarian cancer was investigated using CCK8 assays and colony formation assays in vitro.Nude mouse subcutaneous model was used to study the cancer cell growth in vivo.Results1.The RT-qPCR results showed that the expression of miR-145 in epithelialovarian cancer tissues was significantly lower than that of normal ovarian tissues.In addition,the expression of miR-145 in ovarian cancer cells(A2780,OVCAR-3,SKOV-3 & HO8910)was also lower than that of normal ovarian epithelial cell.Specifically,HO8910 and SKOV-3 cells demonstrated lowest expression levels of miR-145.2.The miR-145 levels in the serums of epithelial ovarian cancer patients were also lower than those of healthy controls(P < 0.01).3.The serum miR-145 expression was closely associated with patients' clinical stage(P < 0.01).However,the serum miR-145 levels were not associated with factors such as age,pathological grade,histological type,lymph node metastasis,and CA125 levels.4.The studied patients were then divided into high expression group(n=25)and low expression group(n=20)according to serum miR-145 levels.Kaplan-Meier analysis showed that miR-145 expression levels were closely associated with patients' progression-free survival(Progress Free Survival,PFS),that is,patients with lower miR-145 expression had a significant shorter PFS than those with higher miR-145 expression.Moreover,patients with low miR-145 expression also demonstrated a shorter overall survival(OS)that those with high miR-145 expression(P < 0.05).5.CCK-8 and colony formation experiments showed that overexpression of miR-145 repressed ovarian cancer cell proliferation.6.Xenograft tumor model experiment showed that overexpression of miR-145 repressed ovarian cancer cell growth in vivo.ConclusionsThe expression of miR-145 was decreased in epithelial ovarian cancer tissues,epithelial ovarian cancer cells and serums of patients with epithelial ovarian cancer.The miR-145 expression was closely associated with patients' clinical stage and was an independent risk factor of patients' prognosis.The functional experiments showedthat overexpression of miR-145 could inhibit the proliferation of ovarian cancer cells thereby suppressing its malignant progression.Therefore,miR-145 may be a novel target for the diagnosis and treatment of ovarian cancer.