干燥综合征合并特发性肺纤维化miRNA表达谱的变化及生物标志物的研究*

目的: 探究干燥综合征合并特发性肺纤维化患者血清中miRNA表达谱之间的差异关系。方法: 选择在云南省第一人民医院确诊为干燥综合征的3例患者作为对照组,平均年龄为(55.67±4.78) 岁,病程为(10.67±1.70)月;3例干燥综合征合并特发性肺纤维化患者作为观察组,平均年龄为(57.67±3.68) 岁,病程为(11.00±2.45) 月;6例患者均为女性。两组基本资料没有差异(P＞0.05)。利用芯片检测两组患者血清中miRNA表达谱的差异。通过GO富集分析,筛选出13个免疫细胞功能相关的聚类;表达差异明显的基因集中于免疫调节的信号通路。采用qRT-PCR验证其中5个表达有差异的miRNA。结果: 芯片检测结果共筛选出差异表达基因13个,其中6个miRNA上调:hsa-miR-6740-5p,hsa-miR-4507,hsa-miR-6775-5p,hsa-miR-4281,hsa-miR-4459,hsa-miR-6089,7个miRNA下调:hsa-miR-6873-3p,hsa-miR-4290,hsa-miR-6858-3p,hsa-miR-574-3p,hsa-miR-92b-3p,hsa-miR-3151-3p,hsa-miR-6886-3p。qRT-PCR结果验证了5个最明显的差异miRNA,结果和芯片趋势一致,差异显著,具有统计学意义。结论: 干燥综合征与干燥综合征合并特发性肺纤维化血清中miRNA表达存在差异,其中miR-6886-3p,miR-6873-3p,miR-574-3p,miR-6740-5p和miR-4507特异性和敏感度较高,可能作为干燥综合征特发性肺纤维化区别于原发性干燥综合征的生物标志物。     

hsa-miR-1249和hsa-miR-486-5p与Ⅱ型糖尿病的相关性研究

microRNAs(miRNAs)是一类普遍存在于真核细胞的非编码小分子RNA,通常在转录后水平抑制靶基因的表达。miRNA表达失调与许多疾病相关,如Ⅱ型糖尿病(T2D)。Ⅱ型糖尿病是一种复杂的疾病,显著特征是高血糖。近年来的研究表明,miRNA在Ⅱ型糖尿病的发生发展中扮演着不同的角色。本研究通过miRNA微阵列芯片和实时荧光定量PCR的方法,发现hsa-miR-1249和hsa-miR-486-5p在Ⅱ型糖尿病患者血浆中较之于正常对照组表达显著降低,显示了hsa-miR-1249和hsa-miR-486-5p可能在Ⅱ型糖尿病的发病过程中起着重要的作用。本研究揭示了hsa-miR-1249和hsa-miR-486-5p有可能成为Ⅱ型糖尿病的新的诊断标志物和治疗靶标。     

hsa-miR-192-3p的靶基因预测及功能分析

通过生物信息学方法预测hsa-miR-192-3p的靶基因及其靶基因的可能功能。首先通过miRbase在线数据库对hsamiR-192-3p的碱基序列及序列在各物种间的保守性进行分析,再通过miRGator v3. 0在线数据库查看hsa-miR-192-3p在各个组织器官中的表达丰富度情况;其次,应用Target Scan和miRanda在线数据库预测hsa-miR-192-3p的靶基因;最后,将预测得到的两个数据库的靶基因交集用DAVID在线数据库进行功能富集分析和信号转导通路富集分析。结果表明:hsa-miR-192-3p在人、家鼠、猕猴等生物中存在高度保守性; hsa-miR-192-3p在胃肠道、肾脏、肝胆系统、干细胞、鼻、脾、胸腺中表达丰富度较高;通过两个靶基因预测软件预测的靶基因取交集后共有190个;功能富集分析发现hsa-miR-192-3p靶基因富集在细胞质、细胞核、质膜、高尔基体等15个细胞组件(p0. 05),参与蛋白结合、GTP酶活性、锌离子跨膜转运蛋白活性等7个分子功能(p0. 05),涉及金属离子运输、RNA聚合酶II启动子的转录阳性调控、基因表达调节、钙离子跨膜运输、胚胎发育等18个生物过程(p0. 05);预测靶基因集合显著富集于癌症通路与催乳素信号通路中(p0. 05)。得出结论:hsa-miR-192-3p预测的靶基因集合富集于多个生物过程,与肿瘤密切相关,生物信息预测为今后的研究奠定了一定的理论基础,为后续实验验证提供了研究方向。     

miRNA调控恶性黑色素瘤细胞上皮-间充质转化的分子网络及机制

黑色素瘤是一种极易发生转移的恶性皮肤肿瘤,具有高度的致死性。上皮-间充质细胞转化(Epithelial-mesenchymal transition, EMT)在胚胎发育过程中起到非常重要的作用,同时在肿瘤的发生和恶化过程中也扮演着重要的角色。miRNA具有广谱的调节能力,对于肿瘤发生和EMT形成都能产生不同程度的影响。本文整合黑色素瘤细胞系转录组和miRNA组测序数据,在转录组数据中筛选得到参与肿瘤EMT过程的基因,通过Mirsystem软件预测并从miRNA组数据中筛选出与之负相关的11个miRNA,包括miR-130a-3p、miR-130b-3p、miR-125a-5p、miR-30a-3p、miR-195-5p、miR-345-5p、miR-509-3-5p、miR-374a-5p、miR-509-5p、miR-148a-3p和miR-330-3p。经过生物信息学分析miRNA靶基因富集的分子网络和信号途径,发现了两个与细胞发育和细胞间相互作用密切相关的网络,以及多个参与调控EMT过程的信号通路。对11个miRNA进行分子生物学验证,发现miR-195-5p、miR-130a-3p、miR-509-5p和miR-509-3-5p共4个可以调节重要肿瘤基因的miRNA。本研究运用mRNA和miRNA两种转录组的测序数据筛选EMT相关miRNA的方法,为肿瘤多组学数据整合分析提供了新的研究思路,并以期能为肿瘤精准基因组学的发展发挥重要的推进作用。     

利用TCGA数据库构建肾透明细胞癌相关miRNA预后模型

利用TCGA数据库中肾透明细胞癌的miRNA与mRNA数据及临床信息,构建由miRNA组成的预后风险评分模型,并筛选与生存预后相关的miRNA-mRNA调控关系对,为研究提供理论依据。下载并整理TCGA[JP+1]数据库中肾透明细胞癌的miRNA与mRNA数据;对数据进行差异分析,将差异表达的miRNA与临床信息进行合并,利用单因素与多因素Cox回归分析,构建预后模型并进行模型评价;对模型中的miRNA进行靶基因预测,结果与差异表达的mRNA进行取交集,构建miRNA-mRNA调控网络;对网络中的mRNA进行生存分析,筛选生存相关的miRNA-mRNA调控关系对。共得到49个差异表达的miRNA与3 613个差异表达的mRNA;预后模型计算公式为:风险值(risk score)=hsa-miR-21-5p表达量×0.603＋hsa-miR-1251-5p表达量×-0.093;调控网络中共纳入31个miRNA-mRNA调控关系对;对mRNA进行生存分析,共得到7个有价值的关系对。所构建预后模型可有效预测肾透明细胞癌患者生存预后情况,筛选到的miRNA-mRNA调控关系对可为相关研究与治疗提供参考。     

星形细胞瘤生存预后相关miRNA-mRNA调控关系对筛选

利用GEO数据库中的芯片数据,筛选与星形细胞瘤生存预后相关的miRNA-mRNA调控关系对,为后续研究提供理论支持。下载芯片数据利用R语言进行差异表达分析,得到星形细胞瘤较正常组织表达显著改变的miRNA与mRNA;通过miRNA靶基因预测,将靶基因与差异表达mRNA取交集,明确mRNA与miRNA之间的关系;利用GEPIA2.0工具在TCGA数据库中筛选有生存价值的mRNA并验证表达情况,利用OncoLnc工具对相应miRNA进行生存分析。筛选到差异表达的miRNA 90个(表达上调22个,下调68个);差异表达的mRNA 644个(表达下调476个,上调168个);根据miRNA靶基因预测结果,整理出miRNA-mRNA关系对30个,对其中的mRNA与miRNA进行生存分析,共得到7个miRNA-mRNA关系对与LGG患者生存预后明显相关,未筛选到与GBM患者生存预后有关的调控关系对。本研究筛选到的7个miRNA-mRNA调控关系对与LGG患者生存预后显著相关,可为相关研究与治疗提供靶点和参考方向。     

Ku70基因稳定敲除HeLa细胞株的建立及其生物学功能研究

目的:利用CRISPR/Cas9技术构建人Ku70基因稳定敲除的HeLa细胞株,并检测其生物学功能。方法:设计并构建向导RNA载体p Cas-g RNA和同源重组供体DNA载体p Back Zero-T-Ku70,2种重组质粒共转染HeLa细胞,加入潮霉素B进行抗性筛选,通过基因组PCR和Western印迹检验Ku70基因是否被敲除;进而,选择Ku70稳定敲除的细胞株,分别采用CCK-8和Transwell实验检测细胞增殖和迁移能力;此外,提取细胞总RNA,反转录成c DNA后用荧光定量PCR仪检测5种miRNA(hsa-miR-649、hsa-miR-544a、hsa-miR-562、hsa-miR-548a、hsa-miR-492)的表达水平。结果:g RNA表达质粒p Cas-g RNA和DNA供体质粒p Back Zero-T-Ku70构建成功;2种重组质粒共转染HeLa细胞,基因组PCR扩增出特异的基因重组DNA片段,Western印迹结果显示Ku70蛋白已基本无表达。细胞增殖和迁移实验显示敲除Ku70基因的HeLa细胞增殖和迁移能力均有所减弱。q RT-PCR结果显示,敲除Ku70基因致hsa-miR-649、hsa-miR-544a和hsa-miR-562水平有所升高,而hsa-miR-548a和hsa-miR-492水平未有明显变化。结论:获得Ku70基因稳定敲除的细胞株;Ku70蛋白可能参与了HeLa细胞增殖和迁移过程;其还可能调节部分miRNA的表达。     

影响BLM基因表达的miRNAs筛选及抑制效率研究

[目的]筛选调控BLM基因表达的miRNAs并研究其抑制效率。[方法]利用Target Scan Human 6.2、microRNA.org、PicTar以及miRsystem在线软件预测调控BLM基因表达的miRNAs;miRNA通过脂质体转染和特异茎环引物反转录、荧光定量PCR及Pfaffl算法检测miRNA对BLM基因表达的影响。[结果]初步筛选出hsa-miR-338-3p为调控BLM基因表达的miRNA;hsa-miR-338-3p抑制效率试验结果表明:当前列腺癌细胞(PC3)转染20μmol/L的hsamiR-338-3p minic时,实验组BLM表达量为对照组的0.44倍,抑制了BLM的表达(P0.01);转染40μmol/L的hsa-miR-338-3p minic时,实验组BLM的表达量为对照组的2.55倍,促进了BLM的表达(P0.01);转染60μmol/L的hsa-miR-338-3p minic时,实验组BLM的表达量为对照组的1.14倍,实验组与对照组差异不显著(P0.05)。[结论]转染20μmol/L、40μmol/L和60μmol/L的hsa-miR-338-3p minic时BLM基因的表达量分别是对照组的0.44倍、2.55倍和1.44倍,转染不同剂量的miRNA对BLM基因的表达情况具有不同的影响。     

癫痫为首发症状的边缘系统胶质瘤的诊断治疗体会(英文)

目的:1.探讨以癫痫为首发症状的胶质瘤的早期诊断和治疗。2了解不同手术方式对疾病的治疗和长期预后的影响。方法:对从2011年8月到2012年9月的31例病人进行回顾性研究分析。结果:病理确诊的WHOⅠ级星形细胞瘤2例,WHOⅠ-Ⅱ级的星形细胞瘤的4例,WHOⅡ级的星形细胞瘤12例,WHOⅡ级少突胶质细胞瘤的7例,WHOⅡ-Ⅲ的星形细胞瘤4例,仅有胶质细胞增生的2例。结论:1以癫痫为首发症状的低级别胶质瘤应诊断明确,注意鉴别诊断。2早期显微手术治疗控制癫痫症状效果较好。3术后给予抗癫痫药物可预防和较少再发作。4根据手术部位,尽可能的全切肿瘤。     

Expression Analyses of MicroRNAs in Hamster Lung Tissues Infected by SARS-CoV-2

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an infectious disease with multiple severe symptoms, such as fever over 37.5°C, cough, dyspnea, and pneumonia. In our research, microRNAs (miRNAs) binding to the genome sequences of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory-related coronavirus (MERS-CoV), and SARS-CoV-2 were identified by bioinformatic tools. Five miRNAs (hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-16-5p, and hsa-miR-196a-1-3p) were found to commonly bind to SARS-CoV, MERS-CoV, and SARS-CoV-2. We also identified miRNAs that bind to receptor proteins, such as ACE2, ADAM17, and TMPRSS2, which are important for understanding the infection mechanism of SARS-CoV-2. The expression patterns of those miRNAs were examined in hamster lung samples infected by SARS-CoV-2. Five miRNAs (hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-221-3p, hsa-miR-140-3p, and hsa-miR-422a) showed differential expression patterns in lung tissues before and after infection. Especially, hsa-miR-15b-5p and hsa-miR-195-5p showed a large difference in expression, indicating that they may potentially be diagnostic biomarkers for SARS-CoV-2 infection.     

A Ten-MicroRNA Signature Identified from a Genome-Wide MicroRNA Expression Profiling in Human Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) is the most common gynecologic malignancy. To identify the micro-ribonucleic acids (miRNAs) expression profile in EOC tissues that may serve as a novel diagnostic biomarker for EOC detection, the expression of 1722 miRNAs from 15 normal ovarian tissue samples and 48 ovarian cancer samples was profiled by using a quantitative real-time polymerase chain reaction (qRT-PCR) assay. A ten-microRNA signature (hsa-miR-1271-5p, hsa-miR-574-3p, hsa-miR-182-5p, hsa-miR-183-5p, hsa-miR-96-5p, hsa-miR-15b-5p, hsa-miR-182-3p, hsa-miR-141-5p, hsa-miR-130b-5p, and hsa-miR-135b-3p) was identified to be able to distinguish human ovarian cancer tissues from normal tissues with 97% sensitivity and 92% specificity. Two miRNA clusters of miR183-96-183 (miR-96-5p, and miR-182, miR183) and miR200 (miR-141-5p, miR200a, b, c and miR429) are significantly up-regulated in ovarian cancer tissue samples compared to those of normal tissue samples, suggesting theses miRNAs may be involved in ovarian cancer development.     

Novel Biomarkers for Non-functioning Invasive Pituitary Adenomas were Identified by Using Analysis of microRNAs Expression Profile

The microRNAs (miRNAs) are involved in multiple pathological processes among various types of tumors. However, the functions of miRNAs in benign brain tumors are largely unexplored. In order to explore the pathogenesis of the invasiveness in non-functional pituitary adenoma (NFPA), the miRNAs expression profile was analyzed between invasive and non-invasive non-functional pituitary adenoma by miRNAs microarray. Six most significant differentially expressed miRNAs were identified including four upregulated miRNAs hsa-miR-181b-5p, hsa-miR-181d, hsa-miR-191-3p, and hsa-miR-598 and two downregulated miRNAs hsa-miR-3676-5p and hsa-miR-383. The functions and corresponding signaling pathways of differentially expressed miRNAs were investigated by bioinformatics techniques, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The result of GO analysis indicates regulation of voltage-gated potassium channel activity, positive regulation of sodium ion transport, positive regulation of GTPase activity, negative regulation of Notch signaling pathway, etc. KEGG pathway reveals a series of biological processes, including prolactin signaling pathway, endocrine and other factor-regulated calcium reabsorption, fatty acid metabolism, neuroactive ligand-receptor interaction, etc. The miRNAs hsa-miR-181a-5p was verified by quantitative real-time PCR, and the expression level was in accordance with the microarray result. Our result can provide the evidence on featured miRNAs which play a prominent role in pituitary adenoma as effective biomarkers and therapeutic targets in the future.     

Dynamic expression of viral and cellular microRNAs in infectious mononucleosis caused by primary Epstein-Barr virus infection in children

Background

Epstein-Barr virus (EBV) was the first virus identified to encode microRNAs (miRNAs). Both of viral and human cellular miRNAs are important in EBV infection. However, the dynamic expression profile of miRNAs during primary EBV infection was unknown. This study aimed to investigate the dynamic expression profile of viral and cellular miRNAs in infectious mononucleosis (IM) caused by primary EBV infection.

Methods

The levels of viral and cellular miRNAs were measured in fifteen pediatric IM patients at three different time-points. Fifteen healthy children who were seropositive for EBV were enrolled in the control group. Relative expression levels of miRNAs were detected by quantitative real-time PCR (qPCR) assay.

Results

EBV-miR-BHRF1-1, 1-2-3P, miR-BART13-1, 19-3p, 11-3P, 12–1, and 16–1 in IM patients of early phase were significantly higher than in healthy children. Most cellular miRNAs of B cells, such as hsa-miR-155-5p, ?34a-5p, ?18b-5p, ?181a-5p, and ?142-5p were up-regulated; while most of cellular miRNAs of CD8?+?T cells, such as hsa-miR-223, ?29c-3p, ?181a, ?200a-3p, miR-155-5p, ?146a, and ?142-5p were down-regulated in IM patients. With disease progression, nearly all of EBV-miRNAs decreased, especially miR-BHRF1, but at a slower rate than EBV DNA loads. Most of the cellular miRNAs of B cells, including hsa-miR-134-5p, ?18b-5p, ?34a-5p, and -196a-5p increased with time. However, most of the cellular miRNAs of CD8?+?T cells, including hsa-let-7a-5p, ?142-3p, ?142-5p, and ?155-5p decreased with time. Additionally, hsa-miR-155-5p of B cells and hsa-miR-18b-5p of CD8+ T cells exhibited a positive correlation with miR-BHRF1-2-5P and miR-BART2-5P (0.96?≤?r?≤?0.99, P?<?0.05). Finally, hsa-miR-181a-5p of B cells had positive correlation with miR-BART4-3p, 4-5P, 16–1, and 22 (0.97?≤?r?≤?0.99, P?<?0.05).

Conclusions

Our study is the first to describe the expression profile of viral and cellular miRNAs in IM caused by primary EBV infection. These results might be the basis of investigating the pathogenic mechanism of EBV-related diseases and bring new insights into their diagnosis and treatment.

     

Circulating miR-23b-3p,miR-145-5p and miR-200b-3p are potential biomarkers to monitor acute pain associated with laminitis in horses

Circulating microRNAs (miRNAs) are emerging as promising biomarkers for several disorders and related pain. In equine practice, acute laminitis is a common disease characterised by intense pain that severely compromises horse welfare. Recently, the Horse Grimace Scale (HGS), a facial expression-based pain coding system, was shown to be a valid welfare indicator to identify pain linked to acute laminitis. The present study aimed to: determine whether miRNAs can be used as biomarkers for acute pain in horses (Equus caballus) affected by laminitis; integrate miRNAs to their target genes and to categorise target genes for biological processes; gather additional evidence on concurrent validity of HGS by investigating how it correlates to miRNAs. Nine horses presenting acute laminitis with no prior treatment were recruited. As control group, nine healthy horses were further included in the experimental design. Samples were collected from horses with laminitis at admission before any treatment (‘pre-treatment’) and 7 days after routine laminitis treatment (‘post-treatment’). The expression levels of nine circulating miRNAs, namely hsa-miR-532-3p, hsa-miR-219-5p, mmu-miR-134-5p, mmu-miR-124a-3p, hsa-miR-200b-3p, hsa-miR-146a-5p, hsa-miR-23b-3p, hsa-miR-145-5p and hsa-miR-181a-5p, were detected and assessed as potential biomarkers of pain by quantitative PCR using TaqMan® probes. The area under the receiver operating curve (AUC) was then used to evaluate the diagnostic performance of miRNAs. Molecular data were integrated with HGS scores assessed by one trained treatment and time point blind veterinarian. The comparative analysis demonstrated that the levels of miR-23b-3p (P=0.029), miR-145-5p (P=0.015) and miR-200b-3p (P=0.023) were significantly higher in pre-treatment and the AUCs were 0.854, 0.859 and 0.841, respectively. MiR-200b-3p decreased after routine laminitis treatment (P=0.043). Combining two miRNAs in a panel, namely miR-145-5p and miR-200b-3p, increased efficiency in distinguishing animals with acute pain from controls. In addition, deregulated miRNAs were positively correlated to HGS scores. Computational target prediction and functional enrichment identified common biological pathways between different miRNAs. In particular, the glutamatergic pathway was affected by all three miRNAs, suggesting a crucial role in the pathogenesis of pain. In conclusion, the dynamic expression of circulating miR-23b-3p, miR-145-5p and miR-200b-3p was detected in horses with acute laminitis and miRNAs can be considered potentially promising pain biomarkers. Further studies are needed in order to assess their relevancy in other painful conditions severely compromising horse welfare. An important implication would be the possibility to use them for the concurrent validation of non-invasive indicators of pain in horses.     

Host microRNAs exhibit differential propensity to interact with SARS-CoV-2 and variants of concern

A significant number of SARS-CoV-2-infected individuals naturally overcome viral infection, suggesting the existence of a potent endogenous antiviral mechanism. As an innate defense mechanism, microRNA (miRNA) pathways in mammals have evolved to restrict viruses, besides regulating endogenous mRNAs. In this study, we systematically examined the complete repertoire of human miRNAs for potential binding sites on SARS-CoV-2 Wuhan-Hu-1, Beta, Delta, and Omicron. Human miRNA and viral genome interaction were analyzed using RNAhybrid 2.2 with stringent parameters to identify highly bonafide miRNA targets. Using publicly available data, we filtered for miRNAs expressed in lung epithelial cells/tissue and oral keratinocytes, concentrating on the miRNAs that target SARS-CoV-2 S protein mRNAs. Our results show a significant loss of human miRNA and SARS-CoV-2 interactions in Omicron (130 miRNAs) compared to Wuhan-Hu-1 (271 miRNAs), Beta (279 miRNAs), and Delta (275 miRNAs). In particular, hsa-miR-3150b-3p and hsa-miR-4784 show binding affinity for S protein of Wuhan strain but not Beta, Delta, and Omicron. Loss of miRNA binding sites on N protein was also observed for Omicron. Through Ingenuity Pathway Analysis (IPA), we examined the experimentally validated and highly predicted functional role of these miRNAs. We found that hsa-miR-3150b-3p and hsa-miR-4784 have several experimentally validated or highly predicted target genes in the Toll-like receptor, IL-17, Th1, Th2, interferon, and coronavirus pathogenesis pathways. Focusing on the coronavirus pathogenesis pathway, we found that hsa-miR-3150b-3p and hsa-miR-4784 are highly predicted to target MAPK13. Exploring miRNAs to manipulate viral genome/gene expression can provide a promising strategy with successful outcomes by targeting specific VOCs.     

MiR-181b-5p Downregulates NOVA1 to Suppress Proliferation,Migration and Invasion and Promote Apoptosis in Astrocytoma

MicroRNAs (miRNAs) are small, short noncoding RNAs that modulate the expression of numerous genes by targeting their mRNA. Numerous abnormal miRNA expression patterns are observed in various human malignancies, and certain miRNAs can act as oncogenes or tumor suppressors. Astrocytoma, the most common neuroepithelial cancer, represents the majority of malignant brain tumors in humans. In our previous studies, we found that the downregulation of miR-181b-5p in astrocytomas is associated with a poor prognosis. The aim of the present study was to investigate the functional role of miR-181b-5p and its possible target genes. miR-181b-5p was significantly downregulated in astrocytoma specimens, and the reduced expression of miR-181b-5p was inversely correlated with the clinical stage. The ectopic expression of miR-181b-5p inhibited proliferation, migration and invasion and induced apoptosis in astrocytoma cancer cells in vitro. The NOVA1 (neuro-oncological ventral antigen 1) gene was further identified as a novel direct target of miR-181b-5p. Specifically, miR-181b-5p bound directly to the 3''-untranslated region (UTR) of NOVA1 and suppressed its expression. In clinical specimens, NOVA1 was overexpressed, and its protein levels were inversely correlated with miR-181b-5p expression. Furthermore, the changing level of NOVA1 was significantly associated with a poor survival outcome. Similar to restoring miR-181b-5p expression, downregulating NOVA1 inhibited cell growth, migration and invasion. Overexpression of NOVA1 reversed the inhibitory effects of miR-181b-5p. Our results indicate that miR-181b-5p is a tumor suppressor in astrocytoma that inhibits tumor progression by targeting NOVA1. These findings suggest that miR-181b-5p may serve as a novel therapeutic target for astrocytoma.     

Altered plasma exosome miRNAs and novel potential biomarkers in pediatric fulminant myocarditis

Previous studies have indicated that exosome-mediated intercellular microRNAs (miRNA) can influence fulminant myocarditis (FM) pathogenesis between immune and cardiac cells. This study explored plasma exosome miRNA profile in pediatric FM using a small RNA microarray. As per our analysis, we observed the differential expression of 266 miRNAs, including 197 upregulated and 69 downregulated candidate genes. Differentially expressed mRNAs in pediatric FM patients' peripheral blood mononuclear cells (PBMCs) were intersected with miRNA target genes predicting tools to screen for FM-specific target genes. The hub genes and their biological and mechanistic pathways related to inflammation and/or the immune system were identified. CeRNA networks of lncRNAs, circRNAs, miRNAs, and mRNAs between cardiomyocytes and PBMCs were finally established. Furthermore, we verified that hsa-miR-146a-5p, hsa-miR-23a-3p, and hsa-miR-27a-3p had higher expression levels in exosomes of pediatric FM patients by qRT-PCR, and hsa-miR-146a-5p shown high sensitivities and specificities for FM diagnosis. Overall, the results demonstrate that the exosome miRNAs play a regulatory role between immune and cardiac cells and provide research targets.