出 处:《河北医药》2021年第20期3055-3059,共5页Hebei Medical Journal
基 金:石家庄市科学研究与发展计划(编号:181461243)。
摘 要:目的检测卵巢上皮性癌组织及多种卵巢细胞系中miR-210的表达,分析miR-210参与的信号通路。方法利用Realtime-PCR方法检测56例卵巢上皮性癌组织及33例正常卵巢组织,及多种卵巢上皮性癌细胞系(HO-8910/HO-8910PM、COC1、OVCAR3、SKOV3/SKOV3-TR30/SKOV3-DDP)中miR-210的表达水平,分析miR-210与卵巢癌患者临床病理学特征及临床预后的关系;应用Target Scan、Pictar、miRanda、miR Base Targets数据库预测miR-210调控的靶基因;应用miRWalk软件中KEGG pathway功能聚类分析miR-210参与的与肿瘤相关的信号通路。结果miR-210在卵巢上皮性癌组织中的相对表达量高于正常卵巢组织(1.539±0.363 VS 1.017±0.289),差异有统计学意义(t=5.438,P<0.001);与人正常卵巢细胞系IOSE386相比,miR-210在卵巢上皮性癌细胞系HO-8910/HO-8910PM、SKOV3/SKOV3-TR30/SKOV3-DDP、COC1、OVCAR3均上调表达(F=12.64,P<0.001)。miR-210的表达在HO-8910 PM高于HO-8910(t=7.328,P=0.0004),SKOV3-TR30高于SKOV3(t=9.869,P=0.0001),SKOV-3/DDP高于SKOV3(t=6.6376,P=0.0006),差异均有统计学意义(P<0.05)。经过分析显示miR-210的高表达与卵巢癌患者的FIGO分期及肿瘤细胞分化程度相关(χ^(2)=8.927,P=0.030;χ^(2)=7.006,P=0.030);miR-210低表达组患者的5年生存率为36.0%,中位生存时间为49个月,miR-210高表达患者的5年生存率为25.8%,中位生存时间为23.5个月,经过Log-Rank检验,miR-210高表达组5年生存率低于低表达组的5年生存率,差异有统计学意义(χ^(2)=5.380,P=0.020)。经靶基因预测可以确定miR-210的可能靶基因为GPD1L、NFKB1、ABCB9、U2AF2、XPA、RAD52等共23个;通过KEGG pathway分析得出miR-210可能参与的信号通路共9条。结论miR-210在卵巢癌组织及多种细胞系中高表达,其可能通过相关的靶基因参与多种信号通路调控卵巢癌的发生、发展,miR-210可以作为卵巢癌预后判断的指标之一。Objective To investigate the expressions of miR-210 in epithelial ovarian cancer cell lines,and to analyze the signal pathway participate by miR-210.Methods A total of 56 cases of epithelial ovarian cancer tissues and 33 cases of normal ovarian tissues,and a variety of epithelial ovarian cancer cell lines HO-8910/HO-8910PM,SKOV3/SKOV3-TR30/SKOV3-DDP,COC1,OVCAR3 were enrolled in the study.The expression levels of miR-210 were detected by RT-PCR to analyze the correlation between miR-210 and clinicopathological characteristics and prognosis of patients with ovarian cancer.Target Scan,Pictar,miRanda,miR Base Targets database were used to predict the target genes regulated by miR-210.Moreover the KEGG pathway function clustering in miRWalk software was used to analyze the tumor-related signaling pathways involved in miR-210.Results The expression levels of miR-210 in ovarian epithelial cancer tissue were significantly higher than those in normal ovarian tissue(P<0.01).Compared with the cell line IOSE386,the expression levels of miR-210 were significantly up-regulated in ovarian epithelial cancer cell lines HO-8910/HO-8910PM,SKOV3/SKOV3-TR30/SKOV3-DDP,COC1,and OVCAR3(P<0.01).The expression levels of miR-210 in HO-8910 PM were significantly higher than those in HO-8910(P<0.01),which in SKOV3-TR30 were significantly higher than those in SKOV3(P<0.01),which in SKOV-3/DDP were significantly higher than those in SKOV3(P<0.01).Moreover the high expression of miR-210 was correlated with FIGO stage and the degree of tumor cell differentiation(P<0.05).In adition the 5-year survival rate in miR-210 low expression group was 36.0%(mediian survival time:49 months),which was significantly higher than that(25.8%)in miR-210 low expression group(P<0.05).According to the prediction of target genes,23 possible target genes for miR-210 were GPD1L,NFKB1,ABCB9,U2AF2,XPA,RAD52 and so on.In addition a total of 9 possible signal pathways for miR-210 might be involved in KEGG pathway analysis.Conclusion The miR-210 is highly expressed in ovari
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