文章摘要
纪奇峰,祝春来,王 伟,毛 壮,汪 钦,成 珊,颜 真.肝细胞癌患者血清外泌体microRNA表达鉴定[J].,2018,(22):4213-4218
肝细胞癌患者血清外泌体microRNA表达鉴定
Exosomal MicroRNA Expression Identification in Hepatocellular Carcinoma Patients Serum
投稿时间:2018-03-23  修订日期:2018-04-18
DOI:10.13241/j.cnki.pmb.2018.22.003
中文关键词: 肝细胞癌  外泌体  miRNAs  肿瘤标志物
英文关键词: Hepatocellular carcinoma  Exosome  miRNAs  Tumor biomarker
基金项目:肿瘤生物学国家重点实验室自由探索项目(CBSKL2015Z14);陕西省科技统筹创新工程项目(2016KTCL03-09)
作者单位E-mail
纪奇峰 第四军医大学药学院药物基因组学教研室 陕西 西安710032肿瘤生物学国家重点实验室 陕西 西安710032 2496914459@qq.com 
祝春来 第四军医大学药学院药物基因组学教研室 陕西 西安710032肿瘤生物学国家重点实验室 陕西 西安710032  
王 伟 肿瘤生物学国家重点实验室 陕西 西安710032第四军医大学药学院药事管理与药物信息学教研室 陕西 西安710032  
毛 壮 第四军医大学学员一旅一营三连 陕西 西安 710032  
汪 钦 第四军医大学药学院药物基因组学教研室 陕西 西安710032肿瘤生物学国家重点实验室 陕西 西安710032  
成 珊 第四军医大学药学院药物基因组学教研室 陕西 西安710032肿瘤生物学国家重点实验室 陕西 西安710032  
颜 真 第四军医大学药学院药物基因组学教研室 陕西 西安710032肿瘤生物学国家重点实验室 陕西 西安710032  
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中文摘要:
      摘要 目的:探讨肝癌细胞外泌体中差异表达的microRNAs(miRNAs)在肝细胞癌(HCC)诊断中的应用价值。方法:通过高通量测序筛选肝癌细胞外泌体中差异表达的miRNAs。实时定量PCR验证差异表达分子;检测差异表达的miRNAs在健康人(Health)、慢性乙型肝炎患者(CHB)、肝硬化患者(LC)及乙型肝炎病毒阳性的肝细胞癌患者(HCC)血清外泌体中的表达。结果:高通量测序筛选到肝癌细胞外泌体中差异表达的miRNA共88种,其中58种表达上调,30种表达下调。选择其中8种差异表达的miRNAs进行qRT-PCR验证,结果显示,此8种miRNAs在细胞上清外泌体、细胞内、癌与癌旁组织中的表达趋势与测序结果一致。miR-221-3p和miR-224-5p在HCC组外泌体中的表达水平显著高于Health组、CHB组和LC组(P<0.01),miR-124-3p和let-7a-5p在HCC组外泌体中的表达水平显著低于其他各组(P<0.05)。四个组中,miR-21-5p、miR-191-5p、miR-34a-5p和miR-122-5p的表达水平不存在显著性差异(P>0.05)。结论:血清外泌体中的miR-221-3p、miR-224-5p、miR-124-3p 和let-7a-5p可能成为肝细胞癌的候选标志物。
英文摘要:
      ABSTRACT Objective: To explore the possible clinical application of differentially expressed exosomal miRNAs in hepatocellular carcinoma (HCC). Methods: The differential expressed miRNAs from HCC cells exosomes were screened by Next Generation Sequenc- ing. The expression levels of differentially expressed miRNAs were confirmed by quantitative real-time PCR and evaluated in healthy controls (Health), hepatitis B patients (CHB), liver cirrhosis patients (LC) and hepatitis B positive HCC patients. Results: Eighty-eight differentially expressed miRNAs were identified in exosomes of HCC cell lines through highthroughput sequencing, including 58 up-reg- ulated and 30 down-regulated miRNAs. Eight differentially expressed miRNAs were verified by qRT-PCR. It showed that miRNA ex- pression was consistent with the sequencing results in either cell line exosomes or in cell lines, also in tumor tissues vs. adjacent tissues. The expression levels of miR-221-3p and miR-224-5p in exosomes were significantly higher in HCC patients than those in Health, CHB or LC group(P<0.01). Furthermore, the expression levels of exosomal miR-124-3p and let-7a-5p were lower in HCC than Health, CHB or LC group(P<0.05). There was no significant difference in the expression of miR-21-5p, miR-191-5p, miR-34a-5p and miR-122-5p among the four groups(P>0.05). Conclusion: Serum exosomal miR-221-3p, miR-224-5p, miR-124-3p and let-7a-5p have the possibility to become canditate biomarkers for hepatocellular carcinoma diagnosis.
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