miR-122在非酒精性肝脏疾病中的作用

正microRNA122(miR-122)是肝脏中一种复杂的特异性microRNA,调节肝脏的多种生理病理过程。miRNAs是长度约为22个核苷酸大小的短的功能性非编码RNA分子,是肝细胞基因网络和通路的调节器,在肝脏疾病的进展中发挥着中心作用~([1])。这种肝脏富集转录因子调控的miRNA能够促进肝细胞的分化并调节脂质代谢,并且在作为抑制肝细胞增殖和恶性转化的抑制因子方面具有显著的活性。大多数miRNAs通过促进或抑制靶基因的翻译来发挥负向调节的作用,少数有促进转录后翻译的作用。miRNA经常发生转录后修饰,这对miR-122 3'端在调节miRNA稳定性方面非常重要。     

MicroRNA与丙型肝炎病毒感染的研究进展

丙型肝炎病毒（HCV）感染是导致慢性肝炎、肝硬化和肝细胞癌的重要原因。近年来的研究发现microRNA在肝脏生理和病理过程中扮演着重要角色。miR-122是肝脏表达量最大的microRNA,在维持肝细胞形态,调节胆固醇代谢,促进HCV感染和维持其RNA水平,抑制肝癌细胞增殖等方面起着重要作用,同时microRNA在抗病毒方面表现出巨大的前景。本文就近年来microRNA在HCV感染方面的研究进展进行综述。     

microRNA与脂肪组织慢性低度炎性反应

脂肪组织慢性低度炎性反应是肥胖、2型糖尿病、高血压、心血管疾病等代谢性疾病的中心环节.研究脂肪组织慢性低度炎性反应的精确调控过程,对于预防和治疗肥胖及相关疾病有重要意义.microRNA是一类非编码RNA,具有调节基因表达的功能.研究显示,microRNA对脂肪组织巨噬细胞、经典炎性反应信号通路及炎性因子、抗炎因子等具有调控作用.     

核受体在脂质代谢过程中的调控作用

核受体是一类配体依赖的转录因子,日前已发现的许多核受体在多种疾病的发生过程中均发挥作用,部分核受体对脂肪酸代谢、胆固醇代谢、胆固醇逆向转运及载脂蛋白的表达具有调控作用．通过调节这些核受体的活性,可达到调节脂质代谢的目的;研究这些核受体的作用机制以及寻找对脂质代谢具有调控作用的孤核受体的配体,对于脂代谢异常和动脉粥样硬化的防治具有重要意义。     

microRNA与胆固醇代谢

microRNA(miRNA)是一种长度约为22个核苷酸的非编码小分子RNA.microRNA通过与靶mRNA的3'端非编码区的种子序列互补配对而在转录后水平上对基因的表达进行调控,microRNA参与生物体内许多复杂的生理过程,如细胞分化、凋亡、个体发育等,并与人类多种疾病如病毒感染、糖尿病、心血管疾病和癌症等密切相关.随着越来越多的microRNA被发现,其在生物体物质代谢方面的调节作用也逐渐被认识.文章将介绍近年采关于microRNA的研究进展及其在胆固醇代谢中的作用及应用前景.     

固醇调节元件结合蛋白与脂质代谢的研究进展

固醇调节元件结合蛋白(SREBP)是重要的核转录因子之一,它能与脂质合酶基因的启动子/增强子的固醇调节元件结合,激活靶基因转录,特异性调控胆固醇和脂肪酸代谢.体内脂质代谢的稳定依赖于SREBP的调节.通过对SREBP作用和调控机制深入了解,将有助于提高对脂质代谢性疾病如糖尿病、高脂血症、脂肪肝、肥胖等的认识以及指导临床治疗.     

脂肪细胞分化的调控通路研究

脂肪细胞分化是一个由多个转录因子共同调控的复杂过程.这些转录因子包括CCAAT增强子结合蛋白(C/EBP)、过氧化物酶体增殖物活化受体(PPAR)家族、Wnt通路、固醇调节元件结合蛋白(SREBP)等.因此,揭示脂肪细胞分化的细胞和分子机制,将为治疗肥胖和代谢综合征提供重要的理论基础.现综述脂肪细胞分化及参与其调控的各...     

mircoRNA122与肝脏疾病之间关系的研究现状

microRNA是近年来的研究热点。microRNA-122(miR-122)高表达于肝脏,其与肝脏疾病的关系日益受到人们的关注。miR-122在基因表达调控中的作用能影响肝脏疾病的进展,通过抑制或者增强miR-122的活性,可改善肝脏功能。此文就miR-122与非酒精性脂肪性肝病、丙型病毒性肝炎、肝细胞癌、急性肝衰竭等肝脏疾病的关系作如下综述。     

中医药防治非酒精性脂肪性肝病的作用机制

目前对于非酒精性脂肪性肝病(NAFLD)发病机制的研究越来越广泛,中医药在NAFLD中的作用机制成为新的研究热点。中医药治疗NAFLD取得好的临床疗效,且具有针对性及灵活性、多层次、多靶点治疗的优势。介绍了中医药在改善胰岛素、调节脂质代谢、抗脂质过氧化、调节细胞因子、调控脂质代谢相关因子及动态平衡、维持肠道微生态平衡等方面的作用,同时分析了中医药研究目前存在的主要问题。     

过氧化体增殖物激活受体与脂质代谢

过氧化体增殖物激活受体是一类细胞核内受体，在脂质人圾细胞分化中发挥重要作用。本文简要叙述过氧化体增殖物激活受体的组织分布、结构、配体及激活物。过氧化体增殖行特派主活受体α主要参与调节脂质代谢，贝特类调脂药物的作用部分通过激活过氧化体增殖物活过氧化体增物激活受体α，进而调控脂蛋白脂酶及载脂蛋白等目标基因的表达来实现。过氧化体增殖物激活受体γ主要与脂肪细胞分化及其成脂作用有关，胰岛素增敏剂作为过氧化体     

Targeting microRNA-122 to Treat Hepatitis C Virus Infection

An important host factor for hepatitis C virus (HCV) is microRNA-122 (miR-122). miR-122 is a liver-specific member of a family of small, non-coding RNA molecules known as microRNAs that play major roles in the regulation of gene expression by direct interaction with RNA targets. miR-122 binds directly to two sites in the 5' untranslated region (UTR) of HCV RNA and positively regulates the viral life cycle. The mechanism by which this regulation occurs is still not fully understood. There has been a great deal of interest in potential therapeutics based on small RNAs, and targeting miR-122 to combat HCV is one of the furthest advanced. Chemical inhibitors of miR-122 can be introduced into mammals intravenously and result in potent and specific knockdown of the microRNA, with no detectable adverse effects on liver physiology. This strategy was recently applied to chimpanzees chronically infected with HCV and resulted in a sustained reduction in viral load in the animals. Inhibition of miR-122 therefore presents a very attractive novel approach to treating HCV, a virus for which improved therapeutics are urgently needed.     

MicroRNAs as components of regulatory networks controlling erythropoiesis

Over the last two decades, the role of microRNAs has been extensively investigated, and it has become clear that these small non-coding RNAs play an essential role in several biological processes including erythropoiesis and that their dysregulation is associated with pathologies. Recent technical innovations have considerably advanced this field and allowed extensive study of microRNA expression and regulation in a variety of cell types. In erythropoiesis, microRNA regulation is involved at defined stages and promotes either stem cell proliferation or erythroid cell differentiation. In this review, while recapitulating the maturation steps of erythroid cells, we discuss the progresses in our understanding of microRNA regulation in the erythroid lineage and their contribution to erythroid disorders.     

长链非编码RNA的竞争性内源RNA调控模式在动脉粥样硬化中的研究进展

动脉粥样硬化是一种缓慢进行性的血管炎症性病变。越来越多的研究表明长链非编码RNA(lncRNA)作为竞争性内源RNA(ceRNA)与微小RNA(miRNA)结合,通过ceRNA网络调控靶基因信使RNA(mRNA)分子的表达水平和功能,在动脉粥样硬化的病理生理过程中发挥重要作用。lncRNA、miRNA和mRNA之间的互作调控机制复杂。本文综述了lncRNA-miRNA-mRNA调控网络在动脉粥样硬化发病机制中的调控关系,阐述该调控网络在内皮细胞功能障碍、血管平滑肌细胞表型转化、巨噬细胞激活以及脂质代谢异常等病变中的重要作用,为动脉粥样硬化临床诊疗提供新思路。     

MicroRNA-339 and microRNA-556 regulate Klotho expression in vitro

Klotho is an anti-aging protein with direct effects on life-span in mice. Klotho functions to regulate pathways classically associated with longevity including insulin/IGF1 and Wnt signaling. Decreased Klotho protein expression is observed throughout the body during the normal aging process. While increased methylation of the Klotho promoter is reported, other epigenetic mechanisms could contribute to age-related downregulation of Klotho expression, including microRNA-mediated regulation. Following in silico identification of potential microRNA binding sites within the Klotho 3′ untranslated region, reporter assays reveal regulation by microRNA-339, microRNA-556, and, to a lesser extent, microRNA-10 and microRNA-199. MicroRNA-339 and microRNA-556 were further found to directly decrease Klotho protein expression indicating that, if upregulated in aging tissue, these microRNA could play a role in age-related downregulation of Klotho messenger RNA. These microRNAs are differentially regulated in cancer cells compared to normal cells and may imply a role for microRNA-mediated regulation of Klotho in cancer.     

MicroRNAs mark in the MLL-rearranged leukemia

MicroRNAs are short noncoding RNAs, known regulators of several signaling pathways cell differentiation and proliferation, development, and apoptosis, which are deregulated in acute leukemia. Mixed lineage leukemia (MLL) gene encodes a protein with histone methyltransferase activity, which is essential for the fine tuning of hematopoietic stem cell development and differentiation through the regulation of HOXA and MEIS1. MLL gene rearrangements characterize both acute myeloid and acute lymphoblastic leukemia associated with poor outcomes. MicroRNAs and MLL rearrangements are in tight association regulating each other expression, affecting cell cycle regulators, and composing complex networks with factors involved in leukemogenesis such as MYC and FLT3. MLL fusion genes are also capable of recruiting DNA methyltransferases at microRNAs promoters controlling their expression through epigenetic changes. Direct drug targeting of MLL has been difficult to achieve, and in this context, microRNA expression modulation represents an attractive approach.