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高能饮食诱导的非酒精性脂肪性肝炎小型猪长链非编码RNA转录组的特征分析

Characterization of long non-coding RNA transcriptome in high-energy diet induced nonalcoholic steatohepatitis minipigs.

作者信息

Xia Jihan, Xin Leilei, Zhu Wenjuan, Li Li, Li Chenxiao, Wang Yanfang, Mu Yulian, Yang Shulin, Li Kui

机构信息

State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, No. 2 Yuanmingyuan West Road, Beijing, 100193, P.R. China.

出版信息

Sci Rep. 2016 Jul 28;6:30709. doi: 10.1038/srep30709.

DOI:10.1038/srep30709
PMID:27466003
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4964571/
Abstract

Today, obesity and nonalcoholic steatohepatitis are a worldwide epidemic, although how these syndromes are regulated with respect to lncRNAs remains largely unknown. Our previous studies have revealed important pathological features and molecular characteristics of nonalcoholic steatohepatitis in the minipig model, and in this study, we analyze the features of lncRNAs and their potential target genes. Minipig samples only from liver were analyzed using next-generation deep sequencing. In total, we obtained 585 million raw reads approximately 70.4 Gb of high quality data. After a strict five-step filtering process, 1,179 lncRNAs were identified, including 89 differentially expressed lncRNAs (P < 0.05) in the experiment group relative to the control group. The cis and trans analysis identified target genes that were enriched for specific GO terms (P < 0.01), including immune processes, chemokine activity, cytokine activity, and G-protein coupled receptor binding, which are closely related to nonalcoholic steatohepatitis. The predicted protein-coding targets of the differentially expressed lncRNAs were further analyzed, such as PPAR, FADS2, DGAT2, ACAA2, CYP2E1, ADH4, and Fos. This study reveals a wealth of candidate lncRNAs involved in NASH and their regulated pathways, which should facilitate further research into the molecular mechanisms of this disorder.

摘要

如今,肥胖症和非酒精性脂肪性肝炎在全球范围内流行,尽管这些综合征在长链非编码RNA(lncRNA)方面是如何被调控的,在很大程度上仍然未知。我们之前的研究已经揭示了小型猪模型中非酒精性脂肪性肝炎的重要病理特征和分子特性,在本研究中,我们分析了lncRNA的特征及其潜在的靶基因。仅对来自肝脏的小型猪样本进行了二代深度测序分析。我们总共获得了约5.85亿条原始读数,约70.4Gb的高质量数据。经过严格的五步过滤过程,鉴定出1179个lncRNA,其中包括实验组相对于对照组有89个差异表达的lncRNA(P < 0.05)。顺式和反式分析确定了在特定基因本体术语(P < 0.01)中富集的靶基因,包括免疫过程、趋化因子活性、细胞因子活性和G蛋白偶联受体结合,这些都与非酒精性脂肪性肝炎密切相关。对差异表达lncRNA的预测蛋白质编码靶标进行了进一步分析,如过氧化物酶体增殖物激活受体(PPAR)、脂肪酸去饱和酶2(FADS2)、二酰基甘油酰基转移酶2(DGAT2)、乙酰辅酶A酰基转移酶2(ACAA2)、细胞色素P450 2E1(CYP2E1)、乙醇脱氢酶4(ADH4)和原癌基因Fos。本研究揭示了大量参与非酒精性脂肪性肝炎的候选lncRNA及其调控途径,这将有助于进一步研究该疾病的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09f/4964571/fd8e31a9d86f/srep30709-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09f/4964571/e4a1fe7d07a9/srep30709-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09f/4964571/d4b068919011/srep30709-f2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09f/4964571/dde76df57ad2/srep30709-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09f/4964571/fd8e31a9d86f/srep30709-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09f/4964571/e4a1fe7d07a9/srep30709-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09f/4964571/d4b068919011/srep30709-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09f/4964571/23c21ed36e0d/srep30709-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09f/4964571/dde76df57ad2/srep30709-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09f/4964571/fd8e31a9d86f/srep30709-f5.jpg

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