大鼠脊髓损伤后MicroRNAs表达谱变化

目的:探究大鼠脊髓损伤后microRNAs表达谱变化。方法:将10只成年SD大鼠随机分为假手术组、模型组,建立脊髓损伤模型。术后采用Basso-Beattie-Bresnahan(BBB)量表进行运动功能评分,苏木精-伊红(HE)染色脊髓组织,通过Illumina高通量测序技术,对前期构建的cDNA文库进行RNA-Seq分析。将测序数据与高粱参考基因组对比后,以P<0.05为条件筛选出差异表达基因,通过GO、KEGG等数据库,对DEGs的功能以及参与的调控路径进行分析,并通过RT-qPCR验证RNA-Seq结果的可靠性。结果:假手术组与模型组BBB评分有显著性差异,HE染色观察到脊髓组织结构受损较为严重,脊髓损伤前后microRNAs表达有显著差异。结论:脊髓损伤许多基因表达失调。

筛选的差异表达microRNAs对猪卵母细胞Npm2基因的表达调控及作用研究

旨在研究卵母细胞中筛选的差异表达microRNAs对Npm2(nucleoplasmin 2)基因的调控作用。本研究采集屠宰场卵巢,收集GV期卵母细胞进行体外成熟培养,收集MⅡ期卵母细胞。使用qPCR检测筛选的差异表达miRNAs在GV、MⅡ期卵母细胞的表达水平;双荧光素酶报告试验验证预测的miRNA是否与靶基因Npm2存在结合位点;在体外成熟培养液中添加miRNAs模拟物/抑制物,验证miRNA对卵母细胞体外成熟和孤雌胚胎体外发育能力的影响。添加最适浓度的miRNAs模拟物/抑制物后,使用花生凝集素染色试验检测皮质颗粒分布和qPCR检测Npm2 mRNA表达水平。结果表明,MⅡ期卵母细胞中miR-150、miR-7138-5p表达显著高于GV期卵母细胞(P<0.05),miR-296-3p、miR-423-3p表达水平极显著低于GV期卵母细胞(P<0.01),表达趋势与测序结果一致。miR-32表达水平无显著差异(P>0.05)。双荧光素酶报告试验结果表明,miR-32、miR-7138-5p、miR-296-3p与Npm2存在结合位点,荧光强度极显著下调(P<0.01);miR-150与Npm2存在结合位点,荧光强度显著下调(P<0.05);miR-296-5p、miR-423-3p与Npm2不存在结合位点,荧光强度无显著变化(P>0.05)。通过在体外成熟培养液中添加不同浓度miRNAs模拟物/抑制物以确定最适浓度,添加miR-32抑制物、miR-296-5p模拟物、miR-296-5p抑制物、miR-423-3p模拟物、miR-423-3p抑制物、miR-7138抑制物、miR-150模拟物、miR-150抑制物后皮质颗粒荧光强度极显著下调(P<0.01);添加miR-296-3p抑制物、miR-7138-5p模拟物后皮质颗粒荧光强度显著下调(P<0.05)。MⅡ期卵母细胞Npm2 mRNA表达量极显著高于GV期卵母细胞,添加最适浓度miR-150、miR-296-3p、miR-296-5p、miR-7138-5p模拟物和/或抑制物Npm2 mRNA表达量与对照组有显著差异(P<0.05),添加miR-32、miR-423-3p模拟物/抑制物后MⅡ期卵母细胞Npm2 mRNA表达量与对照组无显著差异(P>0.05)。筛选的差异miRNA(如miR-296-3p、miR-7138-5p)可能通过调控Npm2表达影响卵母细胞体外成熟及早期胚胎体外发育,可为猪卵母细胞microRNAs与靶基因复杂调控网络研究提供基础。

microRNAs在骨质疏松症发生发展中的研究进展

骨质疏松的发生是由于成骨细胞介导的骨形成和破骨细胞介导的骨吸收平衡被打破,而使骨稳态出现异常。骨稳态调节因子microRNAs作为表观调控因子,通过调控成骨细胞和破骨细胞的相关信号分子的表达,使其在骨代谢中发挥重要作用。本文就microRNAs在骨质疏松症中参与调节维持骨微环境的细胞分化、增殖、自噬和在相关信号分子、相关信号通路的表达等方面最新研究进展进行综述,并总结了microRNAs在骨细胞分化中的作用,突出了microRNAs在代谢性骨疾病中作为治疗靶点的潜力。

MicroRNAs在妇科肿瘤发生发展中的研究进展

microRNAs(miRNAs)是一类小RNA分子,在植物和动物的基因表达调控中发挥着重要作用,miRNAs不参与蛋白质的直接合成,而是转录后基因表达的重要调控因子。它们不仅在身体发育中起着关键作用,也是细胞周期、凋亡和分化的关键调节因子。成熟miRNAs的产生需要几个关键步骤。首先,在细胞核中经由RNA polymerase II(PolII)转录完成聚腺苷酸化和封顶产生primary mi RNAs(Pri-miRNAs)。Pri-miRNAs通过Drosha/DGCR8复合物进一步加工合成hairpin precursor mi RNAs(pre-miRNAs)。Pre-miRNAs通过输出蛋白5(XPO5)输出到细胞质中,并被Dicer切割,在这一过程进行末端环的切割后形成成熟的miRNAs。miRNAs以互补序列结合靶mRNA,发挥调控作用。研究表明,超过30%的蛋白质编码基因受miRNAs调控。miRNAs的失调和功能障碍与人类疾病有关,miRNAs的异常表达被认为是癌症发生的重要过程。本文就microRNAs在妇科肿瘤发生发展中的研究现状进行综述。

microRNAs在帕金森病发病机制中作用研究进展

帕金森病(Parkinson’s disease)发病机制复杂,多种机制已被证明与帕金森病的病理生理机制有关,如α-突触核蛋白的积累、氧化应激、异常细胞凋亡和神经炎症等。微小RNA(MicroRNA,miRNA)是一种由内源性基因编码的非编码单链RNA分子。在过去的十年里,许多研究报道了miRNA在一系列重要的生命过程中发挥作用。此外,大量的动物模型实验和临床研究也发现了miRNA在帕金森病中的失调,并证明miRNA通过不同的途径在帕金森病的发生发展中发挥了重要作用。本文综述了一些参与帕金森病发生发展的重要miRNAs。

microRNAs调节MAPK信号通路防治骨质疏松症研究进展

骨质疏松症是一种常见的、发病以中老年人群为主的代谢性疾病。随着中国人口老龄化趋势不断加剧,探究骨质疏松症的生理病理进展对防治骨质疏松症及相关并发症的产生具有重大意义。microRNAs作为一种调节因子参与多种骨细胞的代谢调节,在与骨质疏松症密切相关的成骨细胞与破骨细胞分化与生成中起着关键因素,被认为是防治骨质疏松症的重要因子。MAPK信号通路作为与骨质疏松症相关的经典信号通路,对延缓骨质疏松症的进展具有重要的作用。研究表明,药物对microRNAs的调节能够起到防治骨质疏松症的作用,并与MAPK信号通路间存在联系。本文基于以上背景,探讨microRNAs与MAPK信号通路之间的相关性,并与骨质疏松症治疗中密切相关的骨细胞相联系,以期为骨质疏松症的治疗和预防提供更多的理论基础。

Potential clinical application of microRNAs in bladder cancer

Bladder cancer(BC)is the tenth most prevalent malignancy globally,presenting significant clinical and societal challenges because of its high incidence,rapid progression,and frequent recurrence.Presently,cystoscopy and urine cytology serve as the established diagnostic methods for BC.However,their efficacy is limited by their invasive nature and low sensitivity.Therefore,the development of highly specific biomarkers and effective noninvasive detection strategies is imperative for achieving a precise and timely diagnosis of BC,as well as for facilitating an optimal tumor treatment and an improved prognosis.microRNAs(miRNAs),short noncoding RNA molecules spanning around 20–25 nucleotides,are implicated in the regulation of diverse carcinogenic pathways.Substantially altered miRNAs form robust functional regulatory networks that exert a notable influence on the tumorigenesis and progression of BC.Investigations into aberrant miRNAs derived from blood,urine,or extracellular vesicles indicate their potential roles as diagnostic biomarkers and prognostic indicators in BC,enabling miRNAs to monitor the progression and predict the recurrence of the disease.Simultaneously,the investigation centered on miRNA as a potential therapeutic agent presents a novel approach for the treatment of BC.This review comprehensively analyzes biological roles of miRNAs in tumorigenesis and progression,and systematically summarizes their potential as diagnostic and prognostic biomarkers,as well as therapeutic targets for BC.Additionally,we evaluate the progress made in laboratory techniques within this field and discuss the prospects.

Exosomal microRNAs in hepatocellular carcinoma,expanding research field

In this editorial we comment on the review by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.Small extracellular vesicles(exosomes)play important roles in the tumor microenvironment.In this review,the authors introduce the following points:(1)The composition and function of exosomal microRNAs(miRNAs)of different cell origins in hepatocellular carcinoma(HCC);(2)the crosstalk between exosomal miRNAs from stromal cells and immune cells in the tumor microenvironment and the progression of HCC;and(3)the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC.In addition,the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC was introduced.In this review,the authors give us an overview of the exosomal RNA and summarize the function of exosomal RNA in HCC,which provides a deeper understanding of exosomal miRNAs to the readers.

MicroRNAs in hepatocellular carcinoma treatment:Charting the path forward

MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like other tumors,seldom occurs in isolation;instead,it evolves within a microenvironment featuring oncogenic and tumor-suppressive elements.When combined with suitable delivery vehicles,miRNA technology provides the capability to directly engage with these elements,thereby hindering tumor formation and progression.Ongoing research in this domain holds the promise of enabling a more efficacious and multi-modal treatment approach for HCC in the near future.

靶向严重急性呼吸系统综合症冠状病毒2的人工microRNAs设计与思考

动植物人工miRNAs(artificial miRNAs,amiRNAs)在抗病毒感染中发挥重要作用。然而,有关amiRNAs靶向抑制重症急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)的相关研究未见报道。目的:本研究旨在设计靶向SARS-CoV-2的amiRNAs,进一步分析amiRNAs对不同变异株的匹配程度。方法:利用Invitrogen Block-iT RNAi Designer成功设计靶向SARS-CoV-2的amiRNAs。结果:分别命名为amiR-Cov23utr-1、2、3、4;其中amiR-Cov23utr-1、3和4在Omicron BA.5/2022中靶向区域序列十分保守;amiR-Cov23utr-2在Omicron BA.5/2022中的靶点缺失。结论:本研初步设计和分析了靶向SARS-CoV-2的amiRNAs,为后续深入研究amiRNAs抗SARS-CoV-2感染提供了重要基础资料。

microRNAs对脑出血后神经炎症影响的研究进展

脑出血后所释放的大量内源性物质和血液中的毒性成分可加剧炎性反应和神经缺损,严重影响脑出血患者预后。microRNAs水平在脑出血后发生变化,可通过多种机制调控神经炎症的功能。文章综述归纳总结了microRNAs对脑出血后神经炎症影响的研究进展,旨在为出血性中风患者发现更有效的治疗方法。A large number of endogenous substances and toxic components in blood released after intracerebral hemorrhage can aggravate inflammatory reaction and neurological damage, which seriously affect the prognosis of patients with intracerebral hemorrhage. The level of microRNAs changes after intracerebral hemorrhage, which can regulate the function of neuroinflammation through various mechanisms. This review summarizes the research progress of the effect of microRNAs on neuroinflammation after intracerebral hemorrhage in order to find more effective treatment methods for patients with hemorrhagic stroke.

MicroRNAs as potential biomarkers for diagnosis of schizophrenia and influence of antipsychotic treatment

Chara cterized by positive symptoms(such as changes in behavior or thoughts,including delusions and hallu cinations),negative symptoms(such as apathy,anhedonia,and social withdrawal),and cognitive impairments,schizophrenia is a chro nic,severe,and disabling mental disorder with late adolescence or early adulthood onset,Antipsychotics are the most commonly used drugs to treat schizophrenia,but those currently in use do not fully reverse all three types of symptoms characte rizing this condition.Schizophrenia is frequently misdiagnosed,resulting in a delay of or inappropriate treatment.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of schizophrenia.The recent studies reviewed included microRNA profiling in blood-and urine-based materials and nervous tissue mate rials.From the studies that had validated the preliminary findings,potential candidate biomarkers for schizophrenia in adults could be miR-22-3p,-30e-5p,-92a-3p,-148b-5p,-181a-3p,-181a-5p,-181b-5p,-199 b-5p,-137 in whole blood,and miR-130b,-193a-3p in blood plasma.Antipsychotic treatment of schizophrenia patients was found to modulate the expression of certain microRNAs including miR-130b,-193a-3p,-132,-195,-30e,-432 in blood plasma.Further studies are warranted with adolescents and young adults having schizophrenia and consideration should be given to using animal models of the disorder to investigate the effect of suppressing or overexpressing specific microRNAs.

microRNAs对心脏电生理特性影响的研究进展

非心脏外科围术期心律失常的发生率4%~20%,而心胸外科围术期心律失常的发生率为10%~30%,其中心脏手术患者围术期心律失常的发生率高达90%。围术期心律失常可延长住院时间,增加患者住院期间的发病率和死亡率。研究表明,心血管疾病中存在的异常表达microRNAs可通过调控离子通道、缝隙连接蛋白及细胞内Ca2+处理蛋白等,参与心脏自律性、兴奋性以及传导性,从而调节心脏电生理稳态和心律失常。本文将主要从心脏电生理失衡的角度综述microRNA与心律失常的研究进展。

基于microRNAs差异分析和网络药理学探讨益母草治疗宫腔粘连相关机制

目的通过microRNAs差异分析、网络药理学及分子对接技术,探讨益母草治疗宫腔粘连(intrauterine adhesion,IUA)的潜在作用靶点及相关机制。方法基于GEO(gene expression omnibus)数据库筛选IUA与健康者的差异miRNA,经multiMiR进行靶基因预测。通过TCMSP(traditional Chinese medicine systems pharmacology)数据库检索益母草有效活性成分及相关靶点,并与miRNA靶基因取交集。利用String平台进行蛋白质互作分析,利用cytoNCA筛选关键靶点。基于R语言进行基因本体(gene ontology,GO)和基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析。利用CB-dock2对关键靶点和活性成分进行分子对接。结果共筛选出与IUA相关的差异miRNA 43个,经靶基因预测后与IUA共有13个交集靶点,GO及KEGG富集分析结果显示,益母草治疗IUA作用机制主要与细胞衰老、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、PI3K-Akt信号通路等有关。益母草3个特征性活性成分是花生四烯酸、山奈酚、槲皮素,可与蛋白互作网络中相对应的靶点蛋白细胞周期蛋白依赖性激酶4(cyclin-dependent kinase 4,CDK4)、芳香烃受体(aryl hydrocarbon receptor,AHR)、原癌基因c-myc编码转录因子、血管内皮生长因子(vascular endothelial growth factor,VEGF)进行分子对接,主要活性成分能够与核心靶点结合,并展现出较好的亲和力。结论益母草治疗IUA是多成分、多靶点、多通路相互作用的结果,进一步证实了益母草治疗IUA的科学性及有效性,为后续实验提供了研究思路。

血清microRNAs预测ST段抬高型心肌梗死患者预后不良的Meta分析

目的:利用Meta分析的方法系统评价血清microRNAs对ST段抬高型心肌梗死(ST-segmentelevationmyocardial infarction,STEMI)患者不良预后的预测价值。方法:计算机检索PubMed、Webof Science、EMbase、the Cochrane Library、中国知网、万方数据、维普数据库和中国生物医学文献数据库,纳入microRNAs预测STEMI预后情况的相关研究,检索时限设定为建库至2023年10月31日。根据诊断性试验研究质量评估量表(quality assessment of diagnostic accuracy studies-2,QUADAS-2)评价文献质量,采用Stata 17.0、RevMan 5.4和Meta-Disc 1.4软件进行Meta分析。结果:本研究共纳入14篇国内外研究,涉及STEMI患者1 816例,包括预后不良患者593例。随机效应模型合并结果显示,血清microRNAs预测STEMI患者不良预后的合并敏感度为0.78(95%CI:0.75~0.82),合并特异度为0.77(95%CI:0.75~0.79),综合受试者工作特征曲线下面积为0.85(95%CI:0.83~0.88)。亚组分析表明不同预后事件、患者是否为急性STEMI、不同样本量可能是造成异质性的原因。Deek's对称性检验表明不存在潜在的发表偏倚(t=1.10,P=0.29)。Fagan's列线图显示,应用血清microRNAs后,STEMI患者不良预后事件被正确预测的概率由50%上升至78%,预后良好患者被误判的概率由50%下降至21%。结论:本研究通过Meta分析的方法,共纳入14篇文献,发现血清microRNAs对STEMI患者不良预后具有一定预测价值,在STEMI患者预后管理中具有较好的应用前景。

microRNAs在儿童呼吸道合胞病毒感染中调控作用的研究进展

呼吸道合胞病毒(RSV)是儿童急性下呼吸道感染最常见的病原体,对儿童的健康构成严重威胁,但其病理机制仍不明确,目前仍然没有有效预防和治疗呼吸道合胞病毒的方法。RSV是具有包膜单负链RNA病毒,编码11种蛋白质,这些蛋白质是诱导气道高反应性(AHR)的关键因素。微小RNA(miRNAs)近来被认为是基因表达调控因子,通过调节炎症反应和免疫细胞功能以及气道上皮细胞的宿主免疫反应,在病毒感染中发挥调控作用。本文综述了miRNAs在RSV感染中调控作用的研究进展,旨在为RSV的致病机制、诊断及治疗提供新思路。

Acquired sensorineural hearing loss,oxidative stress,and microRNAs

Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing loss.The etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental factors.Oxidative stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing loss.Short non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic response.Sensory hair cell death is a central histopathological finding in sensorineural hearing loss.As these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing loss.Ovid EMBASE,Ovid MEDLINE,Web of Science Core Collection,and ClinicalTrials.gov databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical trials.Registe red clinical trials known to the senior author we re also assessed.A total of 222studies were thus identified.After excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text screening.This resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative review.MiRNAs miR-34a and miR-29b levels increase with age in mice.These miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT1p53,and SIRT1/hypoxia-inducible factor 1-alpha signaling pathways resulting in increased apoptosis.Furthermore,hypoxia and oxidative stress had a similar adve rse apoptotic effect,which was inhibited by resve ratrol and a myocardial inhibitorassociated transcript,a miR-29b competing endogenous mRNA.Gentamicin reduced miR-182-5p levels and increased cochlear oxidative stress and cell death in mice-an effect that was corrected by inner ear stem cell-derived exosomes.There is ongoing work seeking to determine if these findings can be effectively translated to humans.

Current Research Status of MicroRNAs in Squamous Cell Carcinoma of the Tongue

Tongue squamous cell carcinoma (TSCC) is the most invasive type of oral malignant tumor, posing a serious threat to human life and health. Its pathogenesis is complex and has a high degree of malignancy. Recurrence and metastasis often lead to poor prognosis. MicroRNAs are a type of single stranded small molecule RNA with only 18 - 25 nucleotides, which can regulate the expression of various genes and participate in the occurrence and development of tumors. Studies have found that microRNA expression profiling can serve as a reliable and stable biological indicator for early diagnosis and prognosis of tumors. This article provides a review of the research status of MicroRNAs in squamous cell carcinoma of the tongue.

Virus-Encoded MicroRNAs Reveal How Ranavirus Interacts with Amphibian Immune Defense

Ranaviruses are harmful viruses that infect amphibians, fish, and reptiles, and have caused particularly devastating declines in amphibian populations. One particular type of ranavirus, called Frog Virus 3 (FV3), has been extensively studied due to its prevalence and impact on amphibians. Previous research has primarily focused on the virus’s genes, but little attention has been given to the non-coding regions of its genome. This article reviews recent studies that reveal the ability of ranaviruses, including FV3, to encode microRNA (miRNA), a type of regulatory RNA. These viral miRNAs play a crucial role in suppressing frog immune genes, modulating the virus-host interaction, and promoting viral infection. Understanding how ranaviruses use miRNAs to control disease progression is essential for addressing the health threat they pose to wildlife and ecosystems.

Targeting therapy for hepatocellular carcinoma by delivering microRNAs as exosomal cargo

Exosomes,the smallest extracellular vesicles,have gained significant attention as key mediators in intercellular communication,influencing both physiological and pathological processes,particularly in cancer progression.A recent review article by Wang et al was published in a timely manner to stimulate future research and facilitate practical developments for targeted treatment of hepatocellular carcinoma using exosomes,with a focus on the origin from which exosomes derive.If information about the mechanisms for delivering exosomes to specific cells is incorporated,the concept of targeted therapy for hepatocellular carcinoma using exosomes could be more comprehensively understood.