MicroRNA profile in HBV-induced infection and hepatocellular carcinoma.

MicroRNA profile in HBV-induced infection and hepatocellular carcinoma.
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HBV 诱导的感染和肝细胞癌中的 MicroRNA 谱。

DOI:
10.1186/s12885-017-3816-1
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发表时间:
2017-12-01
期刊:
影响因子:
3.8
通讯作者:
Dong Q
Dong Q
中科院分区:
医学2区
文献类型:
--
作者:
Wang G;Dong F;Xu Z;Sharma S;Hu X;Chen D;Zhang L;Zhang J;Dong Q

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microRNAs(miRNAs)在细胞生长、凋亡、发育和分化等过程中发挥着重要的调控作用。miRNAs的表达失调与多种人类疾病相关。因此,miRNA标签作为疾病的生物标志物和做出治疗决策是有价值的。B型肝炎病毒(HBV)是肝细胞癌(HCC)的主要危险因素。在此,我们筛选了慢性HBV相关HCC中的miRNA。为了确定与HBV感染相关的HCC发生中的miRNA,我们使用微阵列分析分析了来自HBV阳性和HBV阴性患者的12对HCC和相邻匹配的非HCC组织中的总体miRNA表达谱。在32例HBV阳性和24例HBV阴性的HCC患者样本中通过实时PCR验证了芯片结果。利用miRWalk软件预测miRNAs的潜在候选靶基因。同时预测为两种或更多种miRNA靶的基因进行GO和KEGG途径分析。miRNA调控网络分析使用Influencity Pathway Analysis(IPA)软件进行。8种miRNAs(miR-223、miR-98、miR-15 b、miR-199 a-5 p、miR-19 b、miR-22、miR-451和miR-101)参与HBV无关的HCC,(miR-98、miR-375、miR-335、miR-199 a-5 p和miR-22)参与HBV感染,miR-150、miR-342- 3 p、miR-663、miR-20 b、miR-92 a-3 p、miR-376 c-3 p和miR-92 b在HBV相关HCC中特异性改变。Gene Ontology和KEGG分析预测,这些HBV相关HCC miRNA参与调节:转录、RNA聚合酶II启动子、通过MAPK信号通路的蛋白磷酸化、粘着斑和肌动蛋白细胞骨架。IPA分析还表明,这些miRNAs作用于AGO 2、TP 53、CCND 1和其他11个显著影响HCC发生和HBV感染的基因。我们的数据表明,独特的7个miRNAs表达标签可能参与HBV相关HCC的发展。本文的在线版本(10.1186/s12885-017-3816-1)包含补充材料,可供授权用户使用。
MicroRNAs (miRNAs) exhibit essential regulatory functions related to cell growth, apoptosis, development and differentiation. Dysregulated expression of miRNAs is associated with a wide variety of human diseases. As such miRNA signatures are valuable as biomarkers for disease and for making treatment decisions. Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Here we screened for miRNAs in chronic HBV associated HCC. To determine the miRNAs in HCC occurrence associated with HBV infection, we analyzed global miRNA expression profiles in 12 pairs of HCC and adjacent matched non-HCC tissues from HBV-positive and HBV-negative patients using microarray analyses. The microarray result was validated by real-time PCR in 32 HBV-positive and 24 HBV-negative patient HCC samples. The potential candidate target genes of the miRNAs were predicted by miRWalk software. Genes simultaneously predicted as targets by two or more miRNAs were subjected to GO and KEGG pathway analysis. The miRNA regulatory network analysis was performed using the Ingenuity Pathway Analysis (IPA) software. Eight miRNAs (miR-223, miR-98, miR-15b, miR-199a-5p, miR-19b, miR-22, miR-451, and miR-101) were involved in HBV-unrelated HCC, 5 miRNAs (miR-98, miR-375, miR-335, miR-199a-5p, and miR-22) were involved in HBV infection, and 7 miRNAs (miR-150, miR-342-3p, miR-663, miR-20b, miR-92a-3p, miR-376c-3p and miR-92b) were specifically altered in HBV-related HCC. Gene Ontology and KEGG analyses predict that these HBV-related HCC miRNAs are involved in the regulation of: transcription, RNA polymerase II promoter, phosphorylation of proteins through MAPK signaling pathway, focal adhesion, and actin cytoskeleton. IPA analysis also suggest that these miRNAs act on AGO2, TP53, CCND1, and 11 other genes that significantly influence HCC occurrence and HBV infection. Our data indicates that the unique 7 miRNAs expression signature could be involved in the development HBV- related HCC. The online version of this article (10.1186/s12885-017-3816-1) contains supplementary material, which is available to authorized users.
DOI: 10.1002/j.1460-2075.1995.tb06984.x
发表时间: 1995-01-03
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