MiRNA/mRNA network topology in hepatitis virus B-related liver cirrhosis reveals miR-20a-5p/340-5p as hubs initiating fibrosis.
MiRNA/mRNA network topology in hepatitis virus B-related liver cirrhosis reveals miR-20a-5p/340-5p as hubs initiating fibrosis.
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乙型肝炎病毒相关肝硬化中的 miRNA/mRNA 网络拓扑揭示 miR-20a-5p/340-5p 作为启动纤维化的中枢
DOI：
10.1186/s12920-022-01390-x
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发表时间：
2022-11-14
影响因子：
2.7
通讯作者：
中科院分区：
文献类型：
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作者：
乙型肝炎相关性肝硬化（HBV-LC）的病理生理机制尚不清楚。本研究旨在通过对miRNA/mRNA网络的拓扑分析来探讨疾病机制。从前瞻性队列收集的33个外周血单核细胞样本（LC，n = 9;慢性肝炎B，n = 12;正常对照，n = 12）进行配对miRNA/mRNA测序以鉴定miRNA/mRNA网络。分析网络的拓扑特征和功能含义，以捕获病理生理学上重要的miRNA/mRNA，其表达模式在验证组（LC，n = 15;慢性肝炎B，n = 15;正常对照，n = 10）中得到证实，并且在体外证明了启动纤维化的功能潜力。miRNA/mRNA网络包含158个差异表达（DE）miRNA和442个DE-mRNA之间的3121个相互作用。拓扑分析确定了一个包含99个miRNA/mRNA相互作用的核心模块和两个连接75个DE-mRNA的枢纽节点（miR-20 a-5 p/miR-340- 5 p）。发现核心模块的表达模式沿着疾病进展与伤口愈合、炎症和白细胞迁移的持续增加相关，但与免疫应答和脂质代谢调节的影响相关，与HBV-LC的病理生理学一致。miR-20 a-5 p/miR-340- 5 p在体外参与巨噬细胞极化和肝星状细胞（HSC）活化（THP-1、LX-2细胞系），其表达水平在验证组中得到独立证实。HBV-LC中miRNA/mRNA网络的拓扑分析揭示了纤维化与miR-20 a-5 p/miR-340- 5 p之间的关联，涉及启动巨噬细胞和HSC的激活。应进行进一步的验证以确认HSC/巨噬细胞的激活以及miR-20 a-5 p/miR-340- 5 p与其潜在靶点之间的相互作用，这可能有助于开发HBV-LC的非侵入性预后标志物或干预靶点。在线版本包含补充材料，可通过10.1186/s12920-022-01390-x获取。
The pathophysiology of hepatitis B-related liver cirrhosis (HBV-LC) remains unclear. This study aimed to explore the disease mechanisms using topological analysis of the miRNA/mRNA network. Paired miRNA/mRNA sequencing was performed with thirty-three peripheral blood mononuclear cell samples (LC, n = 9; chronic hepatitis B, n = 12; normal controls, n = 12) collected from a prospective cohort to identify the miRNA/mRNA network. Topological features and functional implications of the network were analyzed to capture pathophysiologically important miRNAs/mRNAs, whose expression patterns were confirmed in the validation group (LC, n = 15; chronic hepatitis B, n = 15; normal controls, n = 10), and functional potentials initiating fibrogenesis were demonstrated in vitro. The miRNA/mRNA network contained 3121 interactions between 158 differentially expressed (DE) miRNAs and 442 DE-mRNAs. The topological analysis identified a core module containing 99 miRNA/mRNA interactions and two hub nodes (miR-20a-5p/miR-340-5p), which connected to 75 DE-mRNAs. The expression pattern along the disease progression of the core module was found associated with a continuous increase in wound healing, inflammation, and leukocyte migration but an inflection of immune response and lipid metabolic regulation, consistent with the pathophysiology of HBV-LC. MiR-20a-5p/miR-340-5p were found involved in macrophage polarization and hepatic stellate cell (HSC) activation in vitro (THP-1, LX-2 cell lines), and their expression levels were confirmed in the validation group independently. Topological analysis of the miRNA/mRNA network in HBV-LC revealed the association between fibrosis and miR-20a-5p/miR-340-5p involving initiating activations of macrophage and HSC. Further validations should be performed to confirm the HSC/macrophage activations and the interactions between miR-20a-5p/miR-340-5p and their potential targets, which may help to develop non-invasive prognostic markers or intervention targets for HBV-LC. The online version contains supplementary material available at 10.1186/s12920-022-01390-x.
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影响因子：
2.7
作者：
Ni WJ;Leng XM
通讯作者：
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