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| 1 | Genetic and epigenetic variants influencing the development of nonalcoholic fatty liver disease显示文摘Nonalcoholic fatty liver disease(NAFLD) is common worldwide.The importance of genetic and epigenetic changes in etiology and pathogenesis of NAFLD has been increasingly recognized.However,the exact mechanism is largely unknown.A large number of single nucleotide polymorphisms(SNPs) related to NAFLD has been documented by candidate gene studies(CGSs).Among these genes,peroxisome proliferatoractivated receptor-γ,adiponectin,leptin and tumor necrosis factor-α were frequently reported.Since the introduction of genome-wide association studies(GWASs),there have been significant advances in our understanding of genomic variations of NAFLD.Patatinlike phospholipase domain containing family member A3(PNPLA3,SNP rs738409,encoding I148M),also termed adiponutrin,has caught most attention.The evidence that PNPLA3 is associated with increased hepatic fat levels and hepatic inflammation has been validated by a series of studies.Epigenetic modification refers to phenotypic changes caused by an adaptive mechanism unrelated to alteration of primary DNA sequences.Epigenetic regulation mainly includes microRNAs(miRs),DNA methylation,histone modifications and ubiquitination,among which miRs are studied most extensively.miRs are small natural single stranded RNA molecules regulating mRNA degradation or translation inhibition,subsequently altering protein expression of target genes.The miR-122,a highly abundant miR accounting for nearly 70% of all miRs in the liver,is significantly under-expressed in NAFLD subjects.Inhibition of miR-122 with an antisense oligonucleotide results in decreased mRNA expression of lipogenic genes and improvement of liver steatosis.The investigation into epigenetic involvement in NAFLD pathogenesis is just at the beginning and needs to be refined.This review summarizes the roles of genetics and epigenetics in the development of NAFLD.The progress made in this field may provide novel diagnostic biomarkers and therapeutic targets for NAFLD management. | Yu-Yuan Li | 2012 | World Journal of Gastroenterology2012，18，45： | 16 |
| 2 | LncRNA HULC通过miR-372/CXCR4轴来调控肝癌细胞的增殖、凋亡与上皮-间质转化显示文摘目的探讨LncRNA HULC通过miR-372/CXCR4轴在肝癌细胞增殖、凋亡与上皮-间质转化(EMT)中的作用。方法在线生物信息学TargetScan数据库预测靶基因;细胞转染建立基因过表达和沉默细胞模型;qRTPCR和Western blot检测基因和蛋白质表达;CCK-8分析用于细胞活力检测;细胞集落形成实验用于分析细胞增殖能力;Annexin V-FITC/PI分析用于细胞凋亡检测;免疫组织化学染色检测蛋白的阳性表达。结果在肝癌组织和肝癌细胞中,HULC和CXCR4表达上调,miR-372表达下调;TargetScan数据库分析和双荧光素酶分析揭示了miR-372与HULC或CXCR4之间的靶向关系;CCK-8分析显示HULC和CXCR4提高细胞活力,miR-372抑制细胞活力;细胞集落形成实验表明,HULC和CXCR4促进细胞增殖,miR-372抑制细胞增殖;细胞流式术结果表明,HULC和CXCR4抑制细胞凋亡,miR-372促进细胞凋亡;Western blot结果表明,HULC和CXCR4抑制E-cadherin表达,促进Vimentin表达,而miR-372促进E-cadherin表达,抑制Vimentin表达。结论HULC抑制miR-372的表达,从而促进CXCR4的表达,因此促进了肝癌细胞的增殖、抑制其凋亡并促进EMT进程。 | 刘远光 刘怀海 | 2020 | 中国比较医学杂志2020，30，10： | 6 |
| 3 | miRNA诊断慢性肝病及肝纤维化价值的研究进展显示文摘肝纤维化是指因各种致病因子作用下,产生以肝星状细胞活化增殖作为中心环节,细胞外基质大量产生和沉积,从而逐渐形成纤维组织,进一步继发破坏正常肝组织为主要特征的病理改变。肝纤维化的过程是可逆的,这是慢性肝病的共同特征。寻找与肝纤维化相关的基因,了解肝纤维化发生、发展的分子遗传学机制,进而为肝纤维化的诊断、治疗提供理论依据,是目前的研究热点。 | 张清清 陆伦根 | 2015 | 诊断学理论与实践2015，14，4： | 4 |
| 4 | 微小RNA在脂肪性肝病研究中的新进展显示文摘微小RNA(microRNA,miRNA)是一类长度约为22个核苷酸的内源性非编码小分子RNA,它通过对目标mRNA的剪切和翻译抑制,在转录后水平对动植物起到重要的调控作用。在细胞增殖、凋亡和分化,肿瘤形成,免疫反应,个体发育等病理生理活动中具有至关重要的作用。近年来研究表明,部分miRNA在NAFLD中有不同程度的差异性表达,此文就miRNA的生物学特征及与NAFLD的关系研究进行概述。 | 万星勇 虞朝辉 厉有名 | 2012 | 国际消化病杂志2012，32，5： | 3 |
| 5 | microRNA在非酒精性脂肪性肝病中的作用显示文摘microRNA(miRNA)是一类长度约为22个核苷酸的内源性非编码小分子RNA,通过影响靶mRNA的稳定性或抑制其翻译,从而对基因进行转录后水平的调控。研究发现,一些miRNA在非酒精性脂肪性肝病患者中出现差异性表达,这些差异性表达有多种功能,包括调节脂质和糖代谢,参与折叠蛋白反应、内质网应激、氧化应激、细胞分化、炎性反应及细胞凋亡。此文就miRNA在非酒精性脂肪性肝病病程中的潜在重要作用进行概述。 | 杨婕 刘朝奇 | 2014 | 生命的化学2014，34，6： | 3 |
| 6 | Elevated miR-33a and miR-224 in steatotic chronic hepatitis Cliver biopsies显示文摘AIM:To assess the expression of selected microRNAs(miRNA) in hepatitis C,steatotic hepatitis C,noninfected steatotic and normal liver tissues.METHODS:The relative expression levels of miR-21,miR-33 a,miR-96,miR-122,miR-125 b,miR-221 and miR-224 were determined in 76 RNA samples isolated from 18 non-steatotic and 28 steatotic chronic hepatitis C(CHC and CHC-Steatosis,respectively) cases,18 non-infected,steatotic liver biopsies of metabolic origin(Steatosis) and 12 normal formalin-fixed paraffin-embedded liver tissues using TaqMan MicroRNA Assays.All CHC biopsy samples were obtained prior to initiating therapy.Patients' serum biochemical values,which included glucose,triglyceride,cholesterol,alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl-transferase(GGT),alkaline phosphatase(AP),were obtained and correlated with relative miRNA expression.RESULTS:When compared with control non-infected liver samples,miR-122 and miR-221 levels were reduced in CHC-Steatosis(P < 0.03) and in CHC,CHCSteatosis and Steatosis(P < 0.01).Alternatively,the expression of miR-33 a and miR-224 were elevated in CHC-Steatosis and Steatosis in comparison to control tissue(P < 0.01).The levels of miR-33 a and miR-224 in CHC-Steatosis(P < 0.02) and miR-224 in Steatosis(P < 0.001) were increased in comparison to CHC samples.By contrast,the expression of miR-21 did not differ statistically between diseased and normal liver samples.Levels of miR-33 a correlated negatively with serum AST and AP levels in Steatosis as well as with necroinflammatory grade in CHC,whereas miR-21 correlated positively with AST in Steatosis and displayed negative correlation with triglyceride level in CHC-Steatosis.In contrast,miRNA levels were not correlated with ALT,GGT,cholesterol levels or fibrosis stage.CONCLUSION:Differences in miRNA expression were observed between CHC and steatotic CHC,CHC and steatotic liver,but not between steatotic CHC and steatotic liver of metabolic origin. | Gabor Lendvai Katalin Jármay Gizella Karácsony Tünde Halász Ilona Kovalszky Kornélia Baghy Tibor Wittmann Zsuzsa Schaff András Kiss | 2014 | World Journal of Gastroenterology2014，20，41： | 2 |
| 7 | MicroRNAs在肝疾病中的表达及通路研究显示文摘MicroRNA(miRNA)是内源性的长度为20~25nt的一类非编码RNA,广泛存在于真核生物体内,具有调节基因表达活性的功能。其在生命活动中起着至关重要的作用,如动植物的生长发育、细胞分化、增殖与凋亡、肿瘤发生与发展等。MiRNA无论在数量上还是功能上,可能都远远超过目前的发现。对其进行深入研究,将有助于对生物体的各种生理、病理机制的理解,并最终为疾病的诊断、判断预后和治疗提供新的思路和理论基础。 | 彭伟 聂晚频 | 2014 | 临床与病理杂志2014，34，1： | 1 |
| 8 | 遗传变异与非酒精性脂肪性肝病研究进展显示文摘非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是一种常见疾病,人们越来越多地认识到遗传和表观遗传变化对于NAFLD发病的重要性,但详细发病机制尚不清楚。国内外已有较多关于基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)与NAFLD发病关系的研究,包括候选基因研究(candidate gene studies,CGSs)和全基因组关联研究(genome-wide association studies,GWASs)。目前,磷脂酶家族成员A3(PNPLA3,SNPrs738409,编码I148M),也称为脂肪滋养蛋白引起广泛关注,许多研究证实了PNPLA3与肝内脂肪含量及炎症相关。表观遗传修饰是指在DNA序列无改变的情况下,基因表型适应性变化。表观遗传学主要包括微小RNA(miRs),DNA甲基化和组蛋白修饰,其中miRs研究是热点。miRs是小单链RNA分子,可以调节mRNA的降解或转录导致靶基因的蛋白表达改变。miR-122在肝脏中分布最多,约占所有肝内miRs的70%,应用反义寡核苷酸抑制miR-122可以导致合成脂肪的基因mRNA表达下降,改善肝内脂肪变。这篇综述总结了基因及表观遗传学在NAFLD发展过程中的作用,此方面的研究将有助于提供NAFLD新的诊断指标和治疗手段。 | 周永健 李瑜元 范建高 | 2012 | 中国医学前沿杂志(电子版)2012，4，7： | 1 |
| 9 | MiR-382促进大鼠正常肝细胞BRL-3A增殖显示文摘目的探讨miR-382对大鼠正常肝细胞BRL-3A增殖和凋亡的影响。方法 BRL-3A细胞瞬时转染miR-382的模拟物和抑制物48 h,MTT法测定细胞活性;流式细胞术检测细胞周期;Real-time PCR检测细胞增殖和凋亡相关基因的表达情况。结果在大鼠BRL-3A细胞中,转染模拟物可以显著增加miR-382的表达,转染抑制物可以显著降低miR-382的表达(P<0.01)。MTT检测表明,miR-382过表达后,BRL-3A细胞活性明显提高;流式细胞术检测表明,miR-382过表达组S期的细胞数明显增加,而miR-382干涉组S期的细胞数明显减少;用Real-time PCR检测细胞增殖/凋亡相关基因mRNA表达水平表明,miR-382过表达后,BRL-3A细胞增殖相关基因增殖细胞核抗原(PCNA)、Bcl-2和Ccnd1的mRNA表达水平上调,细胞凋亡相关基因Caspase-3和Bax的mRNA表达水平下调,而miR-382干涉组与上述结果相反。结论 miR-382通过促进细胞增殖相关基因表达,抑制细胞凋亡相关基因表达而促进大鼠正常肝细胞BRL-3A增殖。 | 高航 张春艳 王凤娟 徐存拴 | 2018 | 解剖学报2018，49，4： | 1 |
| 10 | MicroRNA-29与肝纤维化显示文摘微小RNA(microRNA,miRNAs,miR)是一类在转录后水平进行基因调控的非编码小RNA分子。miRNAs分子参与细胞生长、增殖、信号通路调控以及细胞凋亡等多个环节,与多种癌症发生发展有关。目前许多研究表明miR-29可调控多种靶基因的表达,参与多种纤维化疾病的发生、发展过程,miR-29有望成为肝纤维化基因治疗的新靶点,为阐述肝纤维化的发病机制和临床诊治提供了新思路。本文就miR-29与肝纤维化关系的研究进展做一综述。 | 王晓丹 石慧 肖和杰 张艳琼 | 2014 | 武汉大学学报(医学版)2014，35，3： | 1 |
| 11 | 微小RNA在非酒精性脂肪肝病中调控作用的研究进展显示文摘微小RNA(microRNA,miRNA)是一类具有调控功能的非编码RNA,在生物个体生长、发育和疾病发生过程中发挥着重要作用。近年来有关miRNA在非酒精性脂肪肝病(nonalcoholic fatty liver disease,NAFLD)中的作用研究广受关注,miRNA可通过调控肝脏糖脂代谢、炎症反应和纤维化生成等途径参与NAFLD的发生发展。确定组织或循环中表达量异常的miRNA谱将作为诊断NAFLD的新型生物标记物,并且有望成为治疗NAFLD的新靶标。 | 杨燕 童南伟 | 2019 | 重庆医科大学学报2019，44，12： | 0 |
| 12 | 微RNA与肝脏疾病的研究进展显示文摘微RNAs(miRNAs)是内源性非编码单链RNAs,参与调节mRNA和靶基因的蛋白表达,并在细胞的增殖、分化、发育和代谢等生理过程中发挥重要作用。此文将对miRNAs在病毒性肝炎、脂肪肝、药物性肝炎、原发性胆汁性肝硬化及原发性肝癌等常见肝脏疾病中的研究进展作了综述。 | 李阳 咸建春 耿爱文 肖丽 甘建和 | 2015 | 中华临床感染病杂志2015，8，2： | 0 |
| 13 | An annual topic highlight: Alcohol and liver, 2011显示文摘An annual topic highlight: Alcohol and Liver, 2011, covers the important and new aspects of pathogenesis of alcoholic liver diseases (ALD). It includes broad topics ranging from the exacerbation of ALD by infectious (viral) agents (hepatitis C virus and human immunodeficiency virus) to the influence of alcohol on liver fibrogenesis, lipid rafts, autophagy and other aspects. This issue is recommended for both basic scientists and clinicians who are involved in alcoholic liver research. | Natalia A Osna | 2011 | World Journal of Gastroenterology2011，17，20： | 0 |
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