A micro-RNA expression signature for human NAFLD progression.
A micro-RNA expression signature for human NAFLD progression.
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DOI：
10.1007/s00535-016-1178-0
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发表时间：
2016-10
影响因子：
6.3
通讯作者：
Flynn CR
中科院分区：
文献类型：
--
作者：
Guo Y;Xiong Y;Sheng Q;Zhao S;Wattacheril J;Flynn CR
非酒精性脂肪性肝病（NAFLD）描述了从非酒精性脂肪性肝（NAFL）到非酒精性脂肪性肝炎（NASH）、肝硬化（CIR）到肝细胞癌（HCC）的疾病状况恶化。从分子和生化的角度来看，我们对这种疾病的病因的理解受到疾病表现的广谱性、对疾病易感性因素的透彻理解以及与肝脏重复采样相关的伦理问题的限制。为了更好地了解与疾病进展相关的因素，我们通过下一代RNA测序研究了III类肥胖患者（体重指数≥40 kg/m2）在选择性减肥手术时肝活检中microRNAs （miRNAs）表达的改变。在按疾病严重程度分层的36例肝脏活检标本中，比较了233例miRs、313例转移RNA （trna）和392例杂项小RNA （snorna、snRNA、RNAs）的临床特征和无偏RNA表达谱。通过RT-PCR验证了3种mirna （miR-301a-3p和miR-34a-5p升高，miR-375降低）的丰度随疾病进展而差异调节。没有发现与疾病严重程度相关的trna或杂项rna。在癌症基因组图谱（TCGA）中的134个肝细胞癌（HCC）样本中观察到miR-301a升高和miR-375表达降低的类似模式。我们的分析结果表明，NAFLD的严重程度与肝脏microRNA表达改变的特定模式有关，这种模式可能导致这种疾病的脂质和碳水化合物代谢改变。这三种鉴定的mirna可能被用作NAFLD严重程度的生物标志物。在HCC样本的外部验证队列中，这种microRNA表达模式的持久性表明，特定的microRNA表达模式可能允许和/或维持NAFLD发展为HCC。
The spectrum of nonalcoholic fatty liver disease (NAFLD) describes disease conditions deteriorating from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) to cirrhosis (CIR) to hepatocellular carcinoma (HCC). From a molecular and biochemical perspective, our understanding of the etiology of this disease is limited by the broad spectrum of disease presentations, a thorough understanding of the factors contributing to disease susceptibility, and ethical concerns related to repeat sampling of the liver. To better understand factors associated with disease progression, we investigated by next generation RNA sequencing the altered expression of microRNAs (miRNAs) in liver biopsies of Class III obese subjects (body mass index ≥ 40 kg/m2) biopsied at the time of elective bariatric surgery. Clinical characteristics and unbiased RNA expression profiles for 233 miRs, 313 transfer RNAs (tRNAs) and 392 miscellaneous small RNAs (snoRNAs, snRNA, rRNAs) were compared among 36 liver biopsy specimens stratified by disease severity. The abundance of 3 miRNAs (miR-301a-3p and miR-34a-5p increased and miR-375 decreased) found to be differentially regulated with disease progression was validated by RT-PCR. There were no tRNAs or miscellaneous RNAs identified to be associated with disease severity. Similar patterns of increased miR-301a and decreased miR-375 expression were observed in 134 hepatocellular carcinoma (HCC) samples deposited in The Cancer Genome Atlas (TCGA). Our analysis results suggest that NAFLD severity is associated with a specific pattern of altered hepatic microRNA expression that may drive the altered lipid and carbohydrate metabolism hallmark of this disorder. The three identified miRNAs can be potentially used as biomarkers to access the severity of NAFLD. The persistence of this miRNA expression pattern in an external validation cohort of HCC samples suggests specific microRNA expression patterns may permit and/or sustain NAFLD development to HCC.