在乙型肝炎病毒感染患者的肝活组织检查中的全球微小RNA表

StephenW

Global microRNA expression profiling in the liver biopsies of hepatitis B virus–infected patients suggests specific microRNA signatures for viral persistence and hepatocellular injury
Avishek Kumar Singh
Sheetalnath Babasaheb Rooge
Aditi Varshney
Madavan Vasudevan
Ankit Bhardwaj
Senthil Kumar Venugopal
Nirupama Trehanpati
Manoj Kumar
... See all authors
First published: 30 November 2017
https://doi.org/10.1002/hep.29690

Potential conflict of interest: Nothing to report.

Supported by grants from the Department of Biotechnology, Government of India (BT/PR1250 ... More

Abstract

Hepatitis B virus (HBV) can manipulate the microRNA (miRNA) regulatory networks in infected cells to create a permissive environment for viral replication, cellular injury, disease onset, and its progression. The aim of the present study was to understand the miRNA networks and their target genes in the liver of hepatitis B patients involved in HBV replication, liver injury, and liver fibrosis. We investigated differentially expressed miRNAs by microarray in liver biopsy samples from different stages of HBV infection and liver disease (immune‐tolerant [n = 8], acute viral hepatitis [n = 8], no fibrosis [n = 16], early [F1+F2, n = 19] or late [F3+F4, n = 14] fibrosis, and healthy controls [n = 7]). miRNA expression levels were analyzed by unsupervised principal component analysis and hierarchical clustering. Analysis of miRNA–mRNA regulatory networks identified 17 miRNAs and 18 target gene interactions with four distinct nodes, each representing a stage‐specific gene regulation during disease progression. The immune‐tolerant group showed elevated miR‐199a‐5p, miR‐221‐3p, and Let‐7a‐3p levels, which could target genes involved in innate immune response and viral replication. In the acute viral hepatitis group, miR‐125b‐5p and miR‐3613‐3p were up, whereas miR‐940 was down, which might affect cell proliferation through the signal transducer and activator of transcription 3 pathway. In early fibrosis, miR‐34b‐3p, miR‐1224‐3p, and miR‐1227‐3p were up, while miR‐499a‐5p was down, which together possibly mediate chronic inflammation. In advanced fibrosis, miR‐1, miR‐10b‐5p, miR‐96‐5p, miR‐133b, and miR‐671‐5p were up, while miR‐20b‐5p and miR‐455‐3p were down, possibly allowing chronic disease progression. Interestingly, only 8 of 17 liver‐specific miRNAs exhibited a similar expression pattern in patient sera. Conclusion: miRNA signatures identified in this study corroborate previous findings and provide fresh insight into the understanding of HBV‐associated liver diseases which may be helpful in developing early‐stage disease diagnostics and targeted therapeutics. (Hepatology 2018;67:1695‐1709)

StephenW

在乙型肝炎病毒感染患者的肝活组织检查中的全球微小RNA表达谱提示病毒持续存在和肝细胞损伤的特异性microRNA标记
Avishek Kumar Singh
Sheetalnath Babasaheb Rooge
Aditi Varshney
Madavan Vasudevan
Ankit Bhardwaj
Senthil Kumar Venugopal
Nirupama Trehanpati
Manoj Kumar
...查看所有作者
首次发布：2017年11月30日
https://doi.org/10.1002/hep.29690

潜在的利益冲突：无需报告。

印度政府生物技术部拨款支持（BT / PR1250 ...更多

抽象

乙型肝炎病毒（HBV）可以处理受感染细胞中的微小RNA（miRNA）调控网络，为病毒复制，细胞损伤，疾病发作及其进展创造一个允许的环境。本研究的目的是了解涉及HBV复制，肝损伤和肝纤维化的乙型肝炎患者肝脏中的miRNA网络及其靶基因。我们通过芯片研究了HBV感染和肝病（免疫耐受[n = 8]，急性病毒性肝炎[n = 8]，无纤维化[n = 16]，早期[F1 + F2，n = 19]或晚期[F3 + F4，n = 14]纤维化和健康对照[n = 7]）。通过无监督的主成分分析和层次聚类分析miRNA表达水平。 miRNA-mRNA调控网络的分析鉴定了17个miRNA和18个靶基因与四个不同节点的相互作用，每个节点代表疾病进展期间的阶段特异性基因调节。免疫耐受组显示升高的miR-199a-5p，miR-221-3p和Let-7a-3p水平，其可以靶向涉及先天性免疫应答和病毒复制的基因。在急性病毒性肝炎组，miR-125b-5p和miR-3613-3p升高，而miR-940降低，这可能通过信号转导和转录激活因子3途径影响细胞增殖。在早期纤维化中，miR-34b-3p，miR-1224-3p和miR-1227-3p升高，而miR-499a-5p降低，它们一起可能介导慢性炎症。在晚期纤维化中，miR-1，miR-10b-5p，miR-96-5p，miR-133b和miR-671-5p升高，而miR-20b-5p和miR-455-3p降低，慢性疾病进展。有趣的是，17个肝脏特异性miRNA中只有8个在患者血清中表现出相似的表达模式。结论：本研究中发现的miRNA特征证实了先前的研究结果，并为了解HBV相关的肝脏疾病提供了新的见解，这可能有助于开发早期疾病诊断和靶向治疗。 （Hepatology 2018; 67：1695-1709）