miR-17～92基因簇在宫颈癌、子宫内膜癌与卵巢癌多种细胞系中的表达及意义

摘要

目的 检测宫颈癌、子宫内膜癌与卵巢癌多种细胞系中miR-17～92基因簇的表达,初步探讨miR-17～92基因簇与妇科肿瘤发生的关系.方法 利用实时定量PCR方法配对检测Hela/Siha、Ishikawa/HEC-1A、HO-8910/HO-8910PM、SKOV3/SKOV3-TR30/SKOV3-DDP、COC 1/COC 1-DDP和CAOV3、OVCAR3中miR-17～92基因簇的表达水平；应用miRWalk数据库、miR2Subpath 数据库和KEGG pathway功能聚类分析miR-17～92基因簇调控的靶基因及参与的与肿瘤相关的信号通路.结果 与人脐静脉血管内皮细胞系ECV-304相比,miR-17～92基因簇在宫颈癌细胞系Hela与Siha中均呈下调表达(F=9.86,P＜0.001);在子宫内膜癌细胞系Ishikawa与HEC-1A中均呈上调表达(F=10.35,P＜ 0.005);与人正常卵巢细胞系IOSE386相比,miR-17～92基因簇在卵巢癌细胞系HO-8910、HO-8910PM、COC1、COC1/DDP、CAOV3、OVCAR3、SKOV3、SKOV3-TR30、SKOV3/DDP均呈上调表达(F=12.64,P＜0.001).预测得出miR-17～92基因簇的靶基因为ABCA1、ARHGAP21、BAP1、C10oK46、CCND1、CD4等共30个；通过miR2Subpath数据库富集分析得出miR-17～92基因簇参与的生物学过程共8个,KEGG pathway分析得出miR-17～92基因簇参与的信号通路共11条.结论 miR-17～92基因簇在宫颈癌、子宫内膜癌与卵巢癌多种细胞系中表达,且在生物学行为不同的同一肿瘤细胞系中存在差异表达.miR-17～92基因簇可能通过相关的靶基因和信号通路参与宫颈癌、子宫内膜癌与卵巢癌的发生、发展并影响其生物学行为.%Objective To analyze the expression of miR-17~92 gene clusters in cervical cancer,endometrial carcinoma and ovarian cancer cell lines,so as to explore the relationship between miR-17~92 gene clusters and gynecological tumors. Methods miR-17~92 gene cluster expression levels were detected using real-time polymerase chain reaction (PCR) in Hela/Siha,Ishikawa/HEC-lA,HO-8910/HO-8910 PM, SKOV3/SKOV3-TR30/SKOV3-DDP,COC1/COC1-DDP,CAOV3,and OVCAR3 cells. Target genes of miR-17~92 gene clusters and their participation in the tumor-associated signaling pathways were analyzed by miRWalk database, miR2Subpath database and KEGG pathway function clustering analysis. Results Compared with human umbilical vein endothelial cell line ECV-304,miR-17~92 gene clusters were significantly down-regulated in cervical cancer cell lines Hela and Siha (F =9.86,P < 0.001),up-regulated in endometrial cancer cell lines Ishikawa and HEC-1A(F =10.35,P < 0.005). Compared with normal ovarian cell lineIOSE386,miR-17~92 gene clusters were up-regulated in all ovarian cancer ceU lines HO-8910,HO-8910 PM.COCl ,COC1/DDP,CAOV3,OVCAR3,SKOV3,SKOV3-TR30 and SKOV3/DDP (F = 12.64,P < 0.001). Totally 30 genes including ABCA1 ,ARHGAP21 ,BAP1 ,C10orf46,CCND1,CD4,and etc. were predicted as the target of miR-17~92 gene clusters;miR-17~92 gene clusters may participated in eight biological process as suggested by miR2Subpath database enrichment analysis,and 11 signaling pathways by KEGG pathway analysis. Conclusion miR-17~92 gene clusters were widely expressed in cervical cancer,endometrial carcinoma and ovarian cancer cell lines,and the expression levels can be different in same type of tumor cells with different biological behaviors. miR-17~92 gene clusters may involve in the occurrence and development of cervical cancer,endometrial carcinoma and ovarian cancer,and influence its biological behavior through the related target genes and signaling pathways.