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Evolutionary conservation of long non-coding RNAs in non-alcoholic fatty liver disease

机译:在非酒精性脂肪肝疾病中长期非编码RNA的进化守恒

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Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of conditions ranging from hepatic steatosis to steatohepatitis (NASH) to fibrosis in the absence of alcohol consumption. Its pathogenesis involves both genetic and environmental factors with a multitude of underlying molecular mechanisms and mediators at each stage. Recent transcriptomic-based studies have led to the identification and association of long non-coding RNAs (lncRNAs) with disease pathology in NAFLD patients and in vivo rodent models. However, the knowledge of function of most of the lncRNAs in NAFLD pathology remains obscure. In the current review, we give a comprehensive catalogue of well reported lncRNAs in NAFLD and classify them using sequence and synteny-based evolutionary conservation across rodents, nonhuman primate and human species. The conserved lncRNAs across all the three species may be dissected in larger clinical studies of NAFLD and can be explored as biomarkers and therapeutic targets. In addition, we also review and analyse single nucleotide polymorphisms (SNPs) in these lncRNAs. It adds another facet to the regulatory role of NAFLD-associated lncRNAs and underscores the significance of a novel genetic landscape of non-coding genome in determining the genetic susceptibility of NAFLD.
机译:非酒精性脂肪肝(NAFLD)包括一系列疾病,从肝脂肪变性到脂肪性肝炎(NASH),再到不饮酒时的纤维化。其发病机制涉及遗传和环境因素,在每个阶段都有许多潜在的分子机制和介质。最近基于转录组学的研究已导致NAFLD患者和活体啮齿动物模型中长非编码RNA(lncRNAs)与疾病病理学的识别和关联。然而,对NAFLD病理学中大多数lncRNAs功能的了解仍然不清楚。在目前的综述中,我们对NAFLD中已报道的lncRNAs进行了全面的分类,并使用基于序列和共线的进化保护方法对它们进行了分类,包括啮齿类动物、非人灵长类动物和人类物种。这三个物种中保守的lncRNAs可在NAFLD的更大规模临床研究中进行解剖,并可作为生物标记物和治疗靶点进行探索。此外,我们还回顾和分析了这些lncRNAs中的单核苷酸多态性(SNPs)。它为NAFLD相关lncRNAs的调节作用增加了另一个方面,并强调了非编码基因组的新遗传景观在确定NAFLD遗传易感性方面的重要性。

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