非编码RNA与细胞自噬调控

细胞自噬是真核生物细胞中高度保守的重要代谢途径。该途径是将细胞内有害或不需要的大分子分解并回收,从而使细胞在生长或环境改变导致的应激和压力条件下获得生存优势。近年越来越多的证据表明,非编码RNA,包括微RNA(microRNA,miRNA)和长非编码RNA(long non-coding RNA,lncRNA),在自噬过程中发挥了重要的作用。本文综述了miRNA和lncRNA在多种细胞环境中对细胞自噬的调控机制,并讨论了这些自噬相关的非编码RNA在疾病分子诊断、分类和预后中的作用,及其作为疾病治疗靶标的可能性。     

细胞自噬调控的分子机制研究进展

细胞自噬是一种进化上保守的分解代谢过程,涉及细胞内长寿命蛋白和受损伤细胞器的降解,其在细胞内稳态、肿瘤、心力衰竭、衰老相关性疾病、神经退行性疾病以及传染病等多种生命进程中发挥着重要作用。泛素样蛋白系统、m TOR信号通路、micro RNA、caspase等均参与了细胞自噬调控过程。该文综述了细胞自噬过程、功能和分子调控机制的研究进展,以期有助于研究细胞自噬机理,为治疗心脏疾病(如动脉粥样硬化)、癌症(如乳腺癌)等提供理论基础。     

MicroRNA对缺血性脑卒中自噬调控作用的研究进展

脑卒中可造成严重的脑部损伤,是人类第二大死亡原因。患者中,缺血性脑卒中更为常见,其发病机制复杂,近年的研究提示细胞自噬参与其中。自噬是一种通过自身降解异常蛋白和受损细胞器维持细胞内环境稳态的分解代谢途径,该过程受基因调控,可抵抗缺血性脑卒中造成的缺血缺氧环境,维持存活状态,但过度的自噬也可直接导致细胞死亡。MicroRNA是一种非编码RNA,可通过与mRNA反向结合,从基因水平上调控多种细胞活动。microRNA可通过对自噬过程的调节而参与缺血性脑卒中多种病理过程的调节。但microRNA在缺血性脑卒中自噬过程中的作用还未完全明晰。本文汇总近年来此领域的最新研究进展,旨在为缺血性脑卒中的基础研究与临床应用奠定理论基础。     

MicroRNA与心脏疾病

微RNA（microRNA,miRNA)是小分子非编码调控RNA,含有大约22个核苷酸,可和靶基因mRNA的3′非编码区相互配对结合,在转录后水平负调控靶基因的表达.微RNA调控细胞的生长、代谢、分化和凋亡, 进而参与生物体的生长发育. 研究表明,微RNA参与人类多种生理和病理过程的调控．最近几年,对微RNA表达调控机制及其调控相关疾病的研究取得了诸多显著性的进展, 心脏疾病相关微RNA更加成为研究的热点.此外,一系列基于微RNA治疗心脏疾病的策略方法,例如用反义寡核苷酸抑制微RNA和微RNA补偿的方法,也取得了突破的成果. 总之,微RNA的研究及应用将为心脏疾病的诊断和治疗提供新的途径.     

运动训练调控细胞自噬相关机体功能的分子机制研究进展

细胞自噬是真核细胞中广泛存在的一种自我保护机制,是细胞在应激情况下通过溶酶体或液泡高度保守的降解途径将细胞内异常蛋白和细胞器降解为生物大分子,重新被细胞利用的过程。适度的运动锻炼可以诱导机体多种组织细胞自噬的激活,增强机体的活力,延缓机体的衰老。运动训练可以刺激骨骼肌细胞自噬水平上调,延缓骨骼肌衰老;运动训练作为一种机械性刺激可以通过调节心肌细胞的自噬激活调控长寿命或错误折叠心肌蛋白和受损细胞器的代谢,延缓心肌衰老;此外,细胞自噬与糖尿病、肿瘤、脑血管疾病、衰老及心脏病等密切相关,运动训练可以预防动脉粥样硬化等血管类疾病的发生,也可以通过调控细胞自噬来预防与治疗心脏病、中风、糖尿病等疾病。现主要论述细胞自噬的涵义与分类,细胞自噬不同阶段的分子机制,以及运动训练通过调控细胞自噬相关基因调控骨骼肌、心肌和自噬相关疾病的分子机制,为使用科学的运动训练方式来提高机体功能及预防和治疗疾病提供了理论依据。     

生物节律基因非编码RNA调控机制

节律性的振荡不仅存在于生物节律中枢也存在于外周器官、组织及细胞中,其产生依赖于节律基因的转录、转录后及翻译后水平调控。近几年,生物节律转录后水平调控机制研究成为热点。非编码RNA(ncRNAs)调控组分小RNA(microRNA)与长链非编码RNA(lncRNA)作为参与转录后调控的重要分子,已有研究表明microRNA与lncRNA调控节律基因mRNA与蛋白的相位及振幅。本文概述microRNA与lncRNA参与昼夜节律中枢与外周调控的研究进展,为生物节律转录后调控机制的进一步研究提供参考。     

m6A修饰调控细胞自噬参与雄性生殖疾病研究进展

N⁶-甲基腺苷(N⁶-methyladenosine, m⁶A)修饰是在腺苷核苷酸N⁶位置上发生的甲基化,在多种RNA代谢过程如m RNA剪接、翻译、运输、降解中发挥关键作用,进而对各种生命过程产生广泛影响。细胞自噬是真核细胞在自噬相关基因的调控下通过溶酶体对自身细胞质蛋白质和受损细胞器进行降解的过程。本文总结了m⁶A修饰调控细胞自噬在雄性生殖疾病发生发展过程中的研究进展,旨在为今后m⁶A修饰调节自噬水平在雄性生殖中的调控机理研究提供参考资料,为雄性生殖疾病的治疗策略提供新方向。     

运动：一种双向调控疾病中自噬异常的手段

自噬(autophagy)是一种进化上高度保守的细胞降解过程,它可以完成细胞成分的基本周转,并提供能量和大分子前体以维持生物体的代谢与平衡。近年研究发现,细胞自噬水平的失调与多种疾病的发生和发展密切相关,这一点已在多种疾病动物模型中得到验证。过高或不足的自噬水平都可能导致疾病。运动作为一种与能量代谢及细胞内环境变化密切相关的活动,与细胞自噬过程之间有密切关联。而运动对自噬的调节是一个双向的过程。对于自噬不足或过度引起的疾病,运动可以恢复其正常的自噬功能,并起到改善、延缓疾病进展的作用。当前,对于运动调控疾病背景下异常的自噬水平的理论及机制尚缺乏充分的阐述。深入探索和讨论运动对疾病中异常自噬水平的调节,将有助于我们拓展视野,为更全面地理解运动在预防和改善各种与自噬相关的疾病过程中的潜在机制和作用。因此,本综述分析概括总结了运动改善疾病中过高或不足的自噬水平及运动对疾病的缓解效果,梳理了运动与自噬的双向调控关系,并进一步提炼归纳了运动调控异常自噬水平所涉及的相关信号通路。这为探究运动促进健康的机制及理清运动调控自噬之间的关系提供理论依据与参考。     

细胞自噬与自身免疫性疾病

细胞自噬是依赖溶酶体的细胞内物质分解代谢系统,清除受损细胞器、死亡细胞和蛋白质聚集体,从而对细胞内稳态起到保护作用。自噬功能失调容易导致细胞内自身物质的积累、诱导自身抗体的产生、进而引起自身免疫性疾病。基因组研究表明,细胞自噬相关基因的单核苷酸多态性与自身免疫性疾病的易感性相关。综述了细胞自噬与自身免疫性疾病之间的联系。     

miR-17-92、自噬在肿瘤中的研究进展

micro RNA(mi RNA)是一类在转录后水平调控目的基因表达的功能性小RNA分子。mi R-17-92基因簇是一个高度保守的基因簇,编码6个mi RNAs,分别为:mi R-17、mi R-18a、mi R-19a、mi R-19b-1、mi R-20a和mi R-92a。细胞自噬(autophagy)是将细胞内受损、变性或衰老的蛋白质以及细胞器运输到溶酶体进行消化降解的过程。mi RNA的异常表达可影响自噬水平,从而影响肿瘤的发生发展。研究证明mi R-17-92基因簇与细胞自噬及肿瘤的发生密切相关,有望成为具有潜在价值的肿瘤标志物或肿瘤治疗的新靶点。现对mi R-17-92基因簇与细胞自噬和肿瘤的关系进行综述。     

The MAPK1/3 pathway is essential for the deregulation of autophagy observed in G2019S LRRK2 mutant fibroblasts

The link between the deregulation of autophagy and cell death processes can be essential in the development of several neurodegenerative diseases, such as Parkinson disease (PD). However, the molecular mechanism of deregulation of this degradative process in PD patients is unknown. The leucine-rich repeat kinase 2 (LRRK2) gene is related to PD and its implication in autophagy regulation has been described. Our recent work shows that the presence of the G2019S LRRK2 mutation, one of the most prevalent in LRRK2, is accompanied by a deregulation of autophagy basal levels dependent on the MAPK1/3 (ERK2/1) pathway.     

The MAPK1/3 pathway is essential for the deregulation of autophagy observed in G2019S LRRK2 mutant fibroblasts

The link between the deregulation of autophagy and cell death processes can be essential in the development of several neurodegenerative diseases, such as Parkinson disease (PD). However, the molecular mechanism of deregulation of this degradative process in PD patients is unknown. The leucine-rich repeat kinase 2 (LRRK2) gene is related to PD and its implication in autophagy regulation has been described. Our recent work shows that the presence of the G2019S LRRK2 mutation, one of the most prevalent in LRRK2, is accompanied by a deregulation of autophagy basal levels dependent on the MAPK1/3 (ERK2/1) pathway.     

Autophagy: from basic research to its application in food biotechnology

Autophagy is a catabolic process by which the cytoplasm is sequestered into double-membrane vesicles and delivered to the lysosome/vacuole for breaking down and recycling of the low molecular weight degradation products. The isolation in the yeast Saccharomyces cerevisiae of many of the genes involved in autophagy constituted a milestone in understanding the molecular bases of this pathway. The identification of ortholog genes in other eukaryotic models revealed that the mechanism of autophagy is conserved among all eukaryotes. This pathway has been shown to be involved in a growing number of physiological processes and conversely, its deregulation may contribute to the development of several diseases. Recent reports have also shown that autophagy may play an important role in biotechnological processes related with the food industry. In this review we discuss current knowledge of the molecular mechanism of autophagy, including some applied aspects of autophagy in the field of food biotechnology.     

Ion channels in the regulation of autophagy

Autophagy is a cellular process in which the cell degrades and recycles its own constituents. Given the crucial role of autophagy in physiology, deregulation of autophagic machinery is associated with various diseases. Hence, a thorough understanding of autophagy regulatory mechanisms is crucially important for the elaboration of efficient treatments for different diseases. Recently, ion channels, mediating ion fluxes across cellular membranes, have emerged as important regulators of both basal and induced autophagy. However, the mechanisms by which specific ion channels regulate autophagy are still poorly understood, thus underscoring the need for further research in this field. Here we discuss the involvement of major types of ion channels in autophagy regulation.     

微RNAs与内质网应激信号通路的相互调控作用

内质网应激(endoplasmic reticulum stress,ERS)是为恢复稳态和减轻蛋白质负荷的一种细胞防御性反应.过度激活的ERS可诱导细胞分化、增殖、凋亡和自噬等.微RNAs(microRNAs,miRNAs)作为一种内源性的非编码RNA(non-coding RNA,ncRNA),可通过转录后作用调控...     

MicroRNA-130a inhibits proliferation of vascular smooth muscle cells by suppressing autophagy via ATG2B

Numerous microRNAs participate in regulating the pathological process of atherosclerosis. We have found miR-130a is one of the most significantly down-regulated microRNAs in arteriosclerosis obliterans. Our research explored the function of miR-130a in regulating proliferation by controlling autophagy in arteriosclerosis obliterans development. A Gene Ontology (GO) enrichment analysis of miR-130a target genes indicated a correlation between miR-130a and cell proliferation. Thus, cell cycle, CCK-8 assays and Western blot analysis were performed, and the results indicated that miR-130a overexpression in vascular smooth muscle cells (VSMCs) significantly attenuated cell proliferation, which was validated by an in vivo assay in a rat model. Moreover, autophagy is thought to be involved in the regulation of proliferation. As our results indicated, miR-130a could inhibit autophagy, and ATG2B was predicted to be a target of miR-130a. The autophagy inhibition effect of miR-130a overexpression was consistent with the effect of ATG2B knockdown. The results that ATG2B plasmids and miR-130a mimics were cotransfected in VSMCs further confirmed our conclusion. In addition, by using immunohistochemistry, the positive results of LC3 II/I and ATG2B in the rat model and artery vascular tissues from the patient were in accordance with in vitro data. In conclusion, our data demonstrate that miR-130a inhibits VSMCs proliferation via ATG2B, which indicates that miR-130a could be a potential therapeutic target that regulates autophagy in atherosclerosis obliterans.