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

Xia, Ji‐Han; Xin, Leilei; Zhu, Wei; Li, Li; Li, Chenxiao; Wang, Yanfang; Mu, Yulian; Yang, Shulin; Li, Kui

doi:10.1038/srep30709

Cited by 32 publications

(24 citation statements)

References 47 publications

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“…In contrast to mRNAs, lncRNAs are generally expressed in low amounts, typically an order of magnitude lower than mRNA expression levels 2,5,[8][9][10] . Furthermore, several studies demonstrated that lncRNA expression levels are very noisy, which is a characteristic shared with low count data from massively parallel RNA sequencing [10][11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

Differential gene expression analysis tools exhibit substandard performance for long non-coding RNA–sequencing data

Assefa

Paepe²,

Everaert

et al. 2017

Preprint

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Background Protein-coding RNAs (mRNA) have been the primary target of most transcriptome studies in the past, but in recent years, attention has expanded to include long non-coding RNAs (lncRNA). lncRNAs are typically expressed at low levels, and are inherently highly variable. This is a fundamental challenge for differential expression (DE) analysis. In this study, the performance of 14 popular tools for testing DE in RNA-seq data along with their normalization methods is comprehensively evaluated, with a particular focus on lncRNAs and low abundant mRNAs. Results Thirteen performance metrics were used to evaluate DE tools and normalization methods using simulations and analyses of six diverse RNA-seq datasets. Non-parametric procedures are used to simulate gene expression data in such a way that realistic levels of expression and variability are preserved in the simulated data. Throughout the assessment, we kept track of the results for mRNA and lncRNA separately. All statistical models exhibited inferior performance for lncRNAs compared to mRNAs across all simulated scenarios and analysis of benchmark RNA-seq datasets. No single tool uniformly outperformed the others. Conclusion Overall, the linear modeling with empirical Bayes moderation (limma) and the nonparametric approach (SAMSeq) showed best performance: good control of the false discovery rate (FDR) and reasonable sensitivity. However, for achieving a sensitivity of at least 50%, more than 80 samples are required when studying expression levels in a realistic clinical settings such as in cancer research. About half of the methods showed severe excess of false discoveries, making these methods unreliable for differential expression analysis and jeopardizing reproducible science. The detailed results of our study can be consulted through a user-friendly web application, http://statapps.ugent.be/tools/AppDGE/

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Section: Introductionmentioning

confidence: 99%

Differential gene expression analysis tools exhibit substandard performance for long non-coding RNA–sequencing data

Assefa

Paepe²,

Everaert

et al. 2017

Preprint

View full text Add to dashboard Cite

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“…Under normal conditions, fatty acid β-oxidation in the mitochondria plays an important role in energy homoeostasis, and mitochondrial dysfunction results in a reduction of fatty acid β-oxidation, which is a critical feature of NAFLD. 11) NASH is characterized by intracellular triglyceride (TG) accumulation, liver fat deposition, inflammatory cell infiltration, ballooning of hepatocytes in the liver, and different degrees of fibrosis, 12,13) which result from an imbalance of increased lipids via circulating lipid uptake, de novo lipogenesis, or decreased lipid disposal primarily by FFA oxidation, and it is considered the first hit in the pathogenesis of NAFLD. The plasma FFA composition has been used to provide insight into cellular metabolic pathways.…”

mentioning

confidence: 99%

Therapeutic Effect of Gypenosides on Nonalcoholic Steatohepatitis <i>via</i> Regulating Hepatic Lipogenesis and Fatty Acid Oxidation

Ying

et al. 2017

Biological & Pharmaceutical Bulletin

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Nonalcoholic steatohepatitis (NASH) is the most frequent cause of liver dysfunction and a common global problem. Gypenosides can decrease pathological modifications of high-fat diet-induced rat atherosclerosis; however, its effect and mechanism on NASH remain unclear. In this study, rats were randomly divided into normal control and model groups. Model rats were fed with a high-fat diet and treated with gypenosides, rosiglitazone, or water for 6 weeks. We found that liver tissues showed significant hepatic steatosis and vacuolar degeneration with significantly higher triglyceride (TG), free fatty acid (FFA) and malonyl CoA, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) activities in model group versus normal control group (p<0.01). Liver tissue mRNA and protein levels of sterol regulatory element binding protein-1c (SREBP-1c), carbohydrate response element binding protein (ChREBP), acetyl-CoA carboxylase (ACCase), and stearoyl CoA desaturase enzyme 1 (SCD1) were significantly increased, while the carnitine palmitoyl transferase-1 (CPT-1) level was significantly decreased in the model group versus the normal control group (p<0.01). Pathological changes of hepatic steatosis; body weight and liver wet weight; liver tissue TG, FFA and malonyl CoA concentrations; serum ALT, AST and GGT activities; liver tissue mRNA and protein levels of SREBP-1c, ChREBP, ACCase, and SCD-1 were significantly decreased; protein and mRNA levels of CPT-1 were significantly increased in the gypenosides group versus model group (p<0.01). In conclusion, gypenosides has therapeutic effect on NASH through regulating key transcriptional factors and lipogenic enzymes involved in fatty acid oxidation during hepatic lipogenesis.

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“…Previous studies have reported that IUGR mammals have increased hepatic gluconeogenic capacity, reduced hepatic lipolysis, and reduced fatty acid oxidation [4,42]. In a rat model, intravenous glucose tolerance test (i.v.GTT) indicates that IUGR will impairs its capacity of glucose tolerance [43]. Previous studies have shown that IUGR impairs hepatic mitochondrial oxidative phosphorylation and influences hepatic energy homeostasis [44].…”

Section: Discussionmentioning

confidence: 99%

The Landscape of Non-Coding RNA in an Adult Pig Model of Intrauterine Growth Restriction

Shen

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Intrauterine growth restriction (IUGR) is a risk factor for adult metabolic syndrome, but how this disease is regulated by lncRNAs and circRNAs remains elusive. Methods: Here, we employed adult IUGR and normal pigs as models to evaluate the expression of various global lncRNAs and circRNAs in pig livers using RNA-seq. Results: In total, we obtained 1,162 million raw reads of approximately 104.54 Gb high quality data. After a strict five-step filtering process, 3,368 lncRNAs were identified, including 300 differentially expressed lncRNAs (p < 0.05) in the IUGR group relative to the control group. The cis-regulatory analysis identified target genes that were enriched in specific GO terms and pathways (p < 0.05), including amino acid metabolism, oxidoreductase activity, PPAR signaling pathway, and insulin signaling pathway. These are closely related to the observed phenotypes of increased gluconeogenesis and impaired mitochondrial oxidative phosphorylation in adulthood of the IUGR group. Additionally, we also identified 403 circRNAs, of which 44 were differentially expressed (p < 0.05). Interestingly, our results identified ATF4-miR214-circRNA7964 and TCF7-miR22-3p-circRNA16347 as two competing endogenous networks, which were closely associated with the observed increase in hepatic gluconeogenesis in the IUGR group. Conclusion: Together, this study reveals a multitude of candidate lncRNAs and circRNAs involved in the development of IUGR pigs, which could facilitate further researches on the molecular mechanisms of metabolic syndrome.

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

Cited by 32 publications

References 47 publications

Differential gene expression analysis tools exhibit substandard performance for long non-coding RNA–sequencing data

Differential gene expression analysis tools exhibit substandard performance for long non-coding RNA–sequencing data

Therapeutic Effect of Gypenosides on Nonalcoholic Steatohepatitis <i>via</i> Regulating Hepatic Lipogenesis and Fatty Acid Oxidation

The Landscape of Non-Coding RNA in an Adult Pig Model of Intrauterine Growth Restriction

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