Integrated Analysis of Long Noncoding RNA Expression Profiles in Acute-on-Chronic Liver Failure.

Integrated Analysis of Long Noncoding RNA Expression Profiles in Acute-on-Chronic Liver Failure.
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慢性慢性肝衰竭中长非编码 RNA 表达谱的综合分析

DOI:
10.1155/2021/5387856
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发表时间:
2021
影响因子:
--
通讯作者:
Fu L
Fu L
中科院分区:
生物学3区
文献类型:
--
作者:
Fu X;Cheng D;Ouyang Y;Li Y;Li R;Peng S;Fu L

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慢性B型肝炎病毒(HBV)感染者可发展为慢性加急性肝衰竭(ACLF),病死率高。长链非编码RNA(lncRNA)参与人类疾病,但目前尚不清楚lncRNA是否参与慢性HBV感染向ACLF的进展。因此,本研究旨在系统地识别和表征lncRNA在慢性HBV感染进展为ACLF的发病机制中的景观和分子机制。对5名ACLF和5名HBV感染患者的外周血样本进行了RNA测序(RNA-Seq)。共检测到9733条lncRNA,其中包括406条注释的lncRNA和9327条新的lncRNA。与慢性HBV感染者相比,ACLF患者中共有407个lncRNA表达显著失调。差异表达lncRNA的侧翼蛋白编码基因富含可能有助于ACLF发病机制的途径,如WNT信号通路。此外,通过qRT-PCR验证了9个选择的差异表达lncRNA,表明这9个lncRNA的表达模式与RNA-Seq数据一致。四个选择的差异表达的lncRNA也在另一个患者队列中得到验证,该患者队列包括80名ACLF患者和65名慢性HBV感染患者。异常lncRNA可能用于开发新的诊断ACLF的生物标志物或药物靶点。
People infected with chronic hepatitis B virus (HBV) might progress to acute-on-chronic liver failure (ACLF) with a high fatality rate. Long noncoding RNAs (lncRNAs) are involved in human diseases, but it is unknown whether lncRNAs are involved in the progression of chronic HBV infection to ACLF. Hence, this study is aimed at systemically identifying and characterizing the landscape and the molecular mechanism of lncRNAs in the pathogenesis of chronic HBV infection progress to ACLF. RNA sequencing (RNA-Seq) of peripheral blood samples from 5 ACLF and 5 HBV infection patients was performed. We detected 9733 lncRNAs, including 406 annotated lncRNAs and 9327 novel lncRNAs. A total of 407 lncRNAs were found to be significantly dysregulated in the patients with ACLF as compared with those in the chronic HBV infection patients. The flanking protein-coding genes of differentially expressed lncRNAs were enriched with pathways that might contribute to the pathogenesis of ACLF, such as the WNT signaling pathway. Furthermore, 9 selected differentially expressed lncRNAs validated by the qRT-PCR, showing that the expression patterns of these 9 lncRNAs were consistent with the RNA-Seq data. Four selected differentially expressed lncRNAs were also validated in another patient cohort comprising 80 patients with ACLF and 65 patients with chronic HBV infection. Aberrant lncRNAs might be used to develop novel diagnostic biomarkers or drug targets for ACLF.
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发表时间: 2017-10
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