BACKGROUND & AIMS: :In this study, we have investigated the expression of 87 micro (mi)RNAs in activated CD4(+) T cells cultured in the presence or absence of the immunoregulatory molecule soluble HLA-G (sHLA-G). We observed (i) a decreased miR-451 expression and (ii) an increased miR-210 expression in sHLA-G-treated CD4(+) T cells. By transfecting CD4(+) T cells with miR-210 and miR-451 mimics or inhibitors, we found that sHLA-G-mediated modulation of these miRNAs was not related to sHLA-G-mediated inhibition of (i) proliferation and (ii) CXCR3 expression in CD4(+) T cells. Finally, we investigated the expression of 14 genes targeted by miR-210 or miR-451 in activated CD4(+) T cells, treated or not with sHLA-G. We observed an increased expression of OSR-1 (odd-skipped related 1) and HBP-1 (HMG-box transcription factor 1) and a decreased expression of CXCL16 (chemokine C-X-C motif ligand 16) and C11orf30 (chromosome 11 open reading frame 30) in sHLA-G-treated CD4(+) T cells. In conclusion, sHLA-G triggered a modulation of miRNA expression that may in turn modulate downstream gene expression, thus affecting CD4(+) T-cell function.

背景与目标： : 在这项研究中，我们已经研究了在存在或不存在免疫调节分子可溶性hla-g (shla-g) 的情况下培养的活化的CD4 () T细胞中87个微 (mi) rna的表达。我们观察到 (i) sHLA中miR-451表达降低和 (ii) miR-210表达增加-通过用miR-210和miR-451模拟物或抑制剂转染CD4(+) T细胞，我们发现shla-g介导的这些mirna的调节与shla-g介导的抑制CD4(+) T细胞增殖和CXCR3表达无关。我们研究了miR-210或miR-451靶向的14个基因在活化的CD4(+) T细胞中的表达，用sHLA-G治疗或不治疗。我们观察到OSR-1 (奇数跳过相关1) 和HBP-1 (HMG-box转录因子1) 的表达增加，CXCL16 (趋化因子c-x-c基序配体16) 和C11orf30 (11号染色体开放阅读框30) 的表达减少shla-g处理的CD4(+) T细胞。总之，shla-g触发了miRNA表达的调节，进而可能调节下游基因表达，从而影响CD4 () T细胞功能。

BACKGROUND & AIMS: PURPOSE:Until recently, tissue fibrosis-ultimately leading to permanent scaring-has been considered an irreversible process. However, recent findings indicate that it may be reversible after all. Vesicourethral anastomotic stenosis (VUAS) as fibrous narrowing is a frequent complication after radical prostatectomy with high recurrence rates and requires invasive treatment. The pathophysiology is poorly understood. Therefore, a combined mRNA and miRNA transcription profiling in tissue from VUAS was performed using nCounter technology. METHODS:To assess tissue morphology and fiber composition, histochemical staining was performed. RNA expression of healthy and fibrotic tissue of twelve patients was analyzed using the human miRNA panel v3 and mRNA PanCancer pathway panel on the nCounter gene1 system and qRT-PCR. Differential expression data analysis was performed using the nSolver software implementing the R-based advanced pathway analysis tool. miRWalk2.0 was used for miRNA target prediction. RESULTS:More linearized tissue architecture, increased collagens, and decreased elastic fibers were observed in VUAS samples. 23 miRNAs and 118 protein coding genes were differentially expressed (p < 0.01) in fibrotic tissue. miRNA target prediction and overlap analysis indicated an interaction of the strongest deregulated miRNAs with 29 deregulated mRNAs. Pathway analysis revealed alterations in DNA repair, cell cycle regulation, and TGF-beta signaling. qRT-PCR confirmed differential expression of top deregulated miRNAs and mRNAs. CONCLUSIONS:In VUAS tissue, severe alterations on mRNA and miRNA level are found. These consistent changes give insights into the pathogenesis of VUAS after radical prostatectomy and point to future options for transcriptomics-based risk stratification and targeted therapies.

背景与目标：

BACKGROUND & AIMS: :In bilaterian animals the 3' ends of microRNAs (miRNAs) are frequently modified by tailing and trimming. These modifications affect miRNA-mediated gene regulation by modulating miRNA stability. Here, we analyzed data from three nonbilaterian animals: two cnidarians (Nematostella vectensis and Hydra magnipapillata) and one poriferan (Amphimedon queenslandica). Our analysis revealed that nonbilaterian miRNAs frequently undergo modifications like the bilaterian counterparts: the majority are expressed as different length isoforms and frequent modifications of the 3' end by mono U or mono A tailing are observed. Moreover, as the factors regulating miRNA modifications are largely uncharacterized in nonbilaterian animal phyla, in present study, we investigated the evolution of 3' terminal uridylyl transferases (TUTases) that are known to involved in miRNA 3' nontemplated modifications in Bilateria. Phylogenetic analysis on TUTases showed that TUTase1 and TUTase6 are a result of duplication in bilaterians and that TUTase7 and TUTase4 are the result of a vertebrate-specific duplication. We also find an unexpected number of Drosophila-specific gene duplications and domain losses in most of the investigated gene families. Overall, our findings shed new light on the evolutionary history of TUTases in Metazoa, as they reveal that this core set of enzymes already existed in the last common ancestor of all animals and was probably involved in modifying small RNAs in a similar fashion to its present activity in bilaterians.

背景与目标： : 在双边动物中，microrna (mirna) 的3' 末端经常通过拖尾和修剪来修饰。这些修饰通过调节miRNA稳定性来影响miRNA介导的基因调控。在这里，我们分析了来自三种非双侧动物的数据: 两种刺胞动物 (Nematostella vectensis和Hydra magnipapillata) 和一种poriferan (昆斯兰的两栖动物)。我们的分析表明，非双边mirna经常像双边对应物一样进行修饰: 大多数表示为不同长度的同工型，并且观察到mono U或mono A拖尾对3' 末端的频繁修饰。此外，由于调节miRNA修饰的因素在非双边动物门中基本上没有特征，因此在本研究中，我们研究了3' 末端尿苷基转移酶 (tutase) 的进化，该酶已知参与了双边中miRNA 3' 非模板修饰。对tutase的系统发育分析表明，TUTase1和TUTase6是双边复制的结果，而TUTase7和TUTase4是脊椎动物特定复制的结果。我们还发现，在大多数研究的基因家族中，果蝇特异性基因重复和结构域丢失的数量出乎意料。总的来说，我们的发现为后生动物中tutaase的进化史提供了新的线索，因为它们揭示了这组核心酶已经存在于所有动物的最后一个共同祖先中，并且可能以与其类似的方式参与了小rna的修饰。在双边主义者中目前的活动。

BACKGROUND & AIMS: :Much evidence indicates that various naturally occurring compounds have an anti-cancer effect, but the detailed mechanisms are not well understood. In this study, we selected anti-cancer phytochemicals such as epigallocatechin-3-gallate (EGCG), resveratrol (RES) and α-mangostin (α-M), all of which are well-characterized chemopreventive agents. We sought to elucidate the mechanism of their anti-cancer effects and the synergistic effects obtained by combined treatment with the anti-cancer drug 5-fluorouracil (5-FU) in three human colon cancer cell lines. The numbers of viable cells were consistently decreased by the treatment with EGCG, RES or α-M at more than 10 μM in all three cell lines tested. All compounds mainly induced apoptosis and suppressed the PI3K/Akt signaling pathway. Additionally, α-M, which had the greatest PI3K/Akt-suppressing activity, also suppressed MAP kinase (MAPK)/Erk1/2 signaling. Importantly, the combination treatment with RES and 5-FU induced a remarkably synergistic enhancement of growth inhibition and apoptosis through the additional suppression of the MAPK/Erk1/2 signaling pathway in colon cancer DLD-1 cells. Interestingly, RES increased the intracellular expression level of miR-34a, which down-regulated the target gene E2F3 and its downstream Sirt1, resulting in growth inhibition. These findings indicate that these compounds functioned as chemosensitizers when combined with anti-cancer drugs through the modulation of apoptotic and growth-related signaling pathways. Also, RES exerted its anti-cancer activity in part through a newly defined mechanism, i.e., the miR-34a/E2F3/Sirt1 cascade.

背景与目标： : 许多证据表明，各种天然存在的化合物具有抗癌作用，但详细的机制尚不清楚。在这项研究中，我们选择了抗癌植物化学物质，例如epigallocatechin-3-gallate (EGCG)，白藜芦醇 (RES) 和 α-甘露素 (α-M)，它们都是特征良好的化学预防剂。我们试图阐明其抗癌作用的机制以及通过与抗癌药物5-氟尿嘧啶 (5-FU) 联合治疗在三种人结肠癌细胞系中获得的协同作用。在所有测试的三种细胞系中，通过使用超过10μm的EGCG，RES或 α-M处理，活细胞的数量持续减少。所有化合物均主要诱导细胞凋亡并抑制PI3K/Akt信号通路。此外，具有最大PI3K/Akt抑制活性的 α-M也抑制了MAP激酶 (MAPK)/Erk1/2信号传导。重要的是，RES和5-FU的联合治疗通过额外抑制结肠癌DLD-1细胞中的MAPK/Erk1/2信号通路，诱导生长抑制和凋亡的显著协同增强。有趣的是，RES增加了miR-34a的细胞内表达水平，从而下调了靶基因E2F3及其下游Sirt1，从而导致生长抑制。这些发现表明，当这些化合物与抗癌药物结合时，通过调节凋亡和与生长相关的信号通路发挥化学增敏作用。此外，RES部分地通过新定义的机制，即miR-34a/E2F3/Sirt1级联发挥其抗癌活性。

BACKGROUND & AIMS: :Thymic degeneration and regeneration are regulated by estrogen and androgen. Recent studies have found that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in organ development. In this study, RNA sequencing (RNA-seq) results showed that ovariectomy significantly affected 333 lncRNAs, 51 miRNAs, and 144 mRNAs levels (p < 0.05 and |log2fold change| > 1), and orchiectomy significantly affected 165 lncRNAs, 165 miRNAs, and 208 mRNA levels in the thymus. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differentially expressed genes (DEGs) were closely related to cell development and immunity. Next, we constructed two lncRNA-miRNA-mRNA networks using Cytoscape based on the targeting relationship between differentially expressed miRNAs (DEMs) and DEGs and differentially expressed lncRNAs (DELs) analyzed by TargetScan and miRanda. Besides, we screened DEGs that were significantly enriched in GO and in ceRNA networks to verify their expression in thymocytes and thymic epithelial cells (TECs). In addition, we analyzed the promoter sequences of DEGs, and identified 25 causal transcription factors. Finally, we constructed transcription factor-miRNA-joint target gene networks. In conclusion, this study reveals the effects of estrogen and androgen on the expression of miRNAs, lncRNAs, and mRNAs in mice thymus, providing new insights into the regulation of thymic development by gonadal hormones and non-coding RNAs.

背景与目标： : 胸腺退化和再生受雌激素和雄激素的调节。最近的研究发现长链非编码rna (lncRNAs) 和microRNAs (miRNAs) 参与器官发育。在这项研究中，RNA测序 (RNA-seq) 结果显示，卵巢切除术显著影响333 lncrna、51 mirna和144 mRNA水平 (p <0.05和 | log2fold变化 |> 1)，而睾丸切除术显著影响胸腺中165 lncrna、165 mirna和208 mRNA水平。基因本体论 (GO) 和京都百科全书的基因和基因组 (KEGG) 分析表明，差异表达基因 (DEGs) 与细胞发育和免疫密切相关。接下来，我们根据差异表达的miRNA (DEMs) 和DEGs之间的靶向关系以及targetsca和miRanda分析的差异表达的lncRNA (DELs)，使用Cytoscape构建了两个lncRNA-miRNA-mRNA网络。此外，我们筛选了在GO和ceRNA网络中显着富集的deg，以验证它们在胸腺细胞和胸腺上皮细胞 (TECs) 中的表达。此外，我们分析了DEGs的启动子序列，并鉴定了25个致病转录因子。最后，我们构建了转录因子-miRNA联合靶基因网络。总之，本研究揭示了雌激素和雄激素对小鼠胸腺miRNAs、lncRNAs和mRNAs表达的影响，为性腺激素和非编码rna调控胸腺发育提供了新的见解。

BACKGROUND & AIMS: Background:Circular RNAs (circRNAs) have received considerable attention in human cancer research. However, many circRNAs remain to be detected. In our study, we determined novel circRNAs and investigated their effects on bladder cancer (BCa). Methods:Microarray dataset GSE92675 was downloaded from Gene Expression Omnibus (GEO). Then, we combined computational biology with quantitative real-time polymerase chain reaction (qRT-PCR) to select related circRNAs in BCa. The selected circRNA-microRNA (miRNA)-messenger RNA (mRNA) regulatory subnetwork was determined by Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results:The regulatory network constructed from the microarray dataset (GSE92675) contained 49 differentially expressed circRNAs (DECs). GO and KEGG analyses showed that the MAPK and PI3K-AKT signaling pathways were statistically significant. On the basis of qRT-PCR and the degree value calculated by the cytoHubba plugin of Cytoscape, hsa_circ_0011385 was finally confirmed. The subnetwork around hsa_circ_0011385 was constructed. In addition, we created a protein-protein interaction (PPI) network composed of 67 nodes and 274 edges after removing independent nodes. GO and KEGG analyses showed that hubgenes were involved in cell cycle activities. Moreover, they could be regulated by miRNAs and play an eventful role in BCa pathogenesis. Conclusions:We proposed a novel circRNA-miRNA-mRNA network related to BCa pathogenesis. This network might be a new molecular biomarker and could be used to develop potential treatment strategies for BCa.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Yam tuber is a storage organ, derived from the modified stem. Tuber expansion is a complex process, and depends on the expressions of genes that can be influenced by environmental and endogenous factors. However, little is known about the regulatory mechanism of tuber expansion. In order to identify the genes and miRNAs involved in tuber expansion, we examined the mRNAs and small RNAs in Dioscorea opposita (Chinese yam) cv. Guihuai 16 tuber during its initiation and expansion stages. RESULTS:A total of 14,238 differentially expressed genes in yam tuber at its expansion stage were identified by using RNA sequencing technology. Among them, 5723 genes were up-regulated, and 8515 genes were down-regulated. Functional analysis revealed the coordination of tuber plant involved in processes of cell events, metabolism, biosynthesis, and signal transduction pathways at transcriptional level, suggesting that these differentially expressed genes are somehow involved in response to tuber expansion, including CDPK, CaM, CDL, SAUR, DELLA, SuSy, and expansin. In addition, 541 transcription factor genes showed differential expression during the expansion stage at transcriptional level. MADS, bHLH, and GRAS were involved in cell differentiation, division, and expansion, which may relate to tuber expansion. Noteworthy, data analysis revealed that 22 known tuber miRNAs belong to 10 miRNA families, and 50 novel miRNAs were identified. The integrated analysis of miRNA-mRNA showed that 4 known miRNAs and 11 genes formed 14 miRNA-target mRNA pairs were co-expressed in expansion stage. miRNA160, miRNA396, miRNA535 and miRNA5021 may be involved in complex network to regulate cell division and differentiation in yam during its expansion stage. CONCLUSION:The mRNA and miRNA datasets presented here identified a subset of candidate genes and miRNAs that are putatively associated with tuber expansion in yam, a hypothetical model of genetic regulatory network associated with tuber expansion in yam was put forward, which may provide a foundation for molecular regulatory mechanism researching on tuber expansion in Dioscorea species.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:The study of microRNAs (miRNAs) is attracting great considerations. Recent studies revealed that miRNAs play as important regulators of gene expression and some even as cancer players or inhibitors. Many studies try to discover new miRNAs and reveal the miRNA expression profile in cancer using a SAGE-based total RNA clone method. However, the data processing of this method is labor-intensive with several different biological databases and more than ten data processing steps involved. RESULTS:With miRAS, miRNAs and possible miRNA candidates contained in the submitted sequencing data were obtained together with their expression profile. The functions of known and predicted miRNAs were then analyzed by miRNA target prediction followed by target gene annotations. Finally, to extract the biological significance of the miRNAs in the samples, further annotations of the known miRNA and target genes were performed by collecting the public expression datasets of miRNA and target genes in normal and cancer tissues. CONCLUSION:We introduce a web-based analysis platform called miRNA Analysis System (miRAS), for processing and analyzing of the sequence data obtained from the total RNA clone method. The system was built on generalizing the study of a liver cancer cell line total RNA sequencing project. miRAS is freely available on the web.

背景与目标：

BACKGROUND & AIMS: :mRNA expression dynamics promote and maintain the identity of somatic tissues in living organisms; however, their impact in post-transcriptional gene regulation in these processes is not fully understood. Here, we applied the PAT-Seq approach to systematically isolate, sequence, and map tissue-specific mRNA from five highly studied Caenorhabditis elegans somatic tissues: GABAergic and NMDA neurons, arcade and intestinal valve cells, seam cells, and hypodermal tissues, and studied their mRNA expression dynamics. The integration of these datasets with previously profiled transcriptomes of intestine, pharynx, and body muscle tissues, precisely assigns tissue-specific expression dynamics for 60% of all annotated C. elegans protein-coding genes, providing an important resource for the scientific community. The mapping of 15,956 unique high-quality tissue-specific polyA sites in all eight somatic tissues reveals extensive tissue-specific 3'untranslated region (3'UTR) isoform switching through alternative polyadenylation (APA) . Almost all ubiquitously transcribed genes use APA and harbor miRNA targets in their 3'UTRs, which are commonly lost in a tissue-specific manner, suggesting widespread usage of post-transcriptional gene regulation modulated through APA to fine tune tissue-specific protein expression. Within this pool, the human disease gene C. elegans orthologs rack-1 and tct-1 use APA to switch to shorter 3'UTR isoforms in order to evade miRNA regulation in the body muscle tissue, resulting in increased protein expression needed for proper body muscle function. Our results highlight a major positive regulatory role for APA, allowing genes to counteract miRNA regulation on a tissue-specific basis.

背景与目标： : mRNA表达动力学促进并维持活生物体中体细胞组织的身份; 但是，它们在这些过程中对转录后基因调控的影响尚未完全了解。在这里，我们应用PAT-Seq方法从五个高度研究的秀丽隐杆线虫体细胞组织中系统地分离、测序和定位组织特异性mRNA: gaba能和NMDA神经元、拱廊和肠瓣细胞、接缝细胞和皮下组织，并研究了它们的mRNA表达动力学。将这些数据集与先前描述的肠，咽和身体肌肉组织的转录组进行整合，精确地为所有注释的秀丽隐杆线虫蛋白质编码基因的60% 分配了组织特异性表达动力学，为科学界提供了重要的资源。在所有八个体细胞组织中15,956独特的高质量组织特异性polyA位点的作图揭示了通过替代多腺苷酸化 (APA) 进行广泛的组织特异性3' 非翻译区 (3'UTR) 同工型转换。几乎所有普遍转录的基因都使用APA，并在其3'utr中携带miRNA靶标，这些靶标通常以组织特异性方式丢失，这表明广泛使用通过APA调节的转录后基因调控来微调组织特异性蛋白表达。在该池中，人类疾病基因C. elegans直系同源物rack-1和tct-1使用APA切换到较短的3'UTR同工型，以逃避身体肌肉组织中的miRNA调节，导致适当的身体肌肉功能所需的蛋白质表达增加。我们的结果强调了APA的主要积极调节作用，允许基因在组织特异性的基础上抵消miRNA的调节。

BACKGROUND & AIMS: :MicroRNAs play an important role in tumor development and progression. Tumor growth is closely associated with glucose metabolism. Specifically, tumor cells produce energy (ATP) under aerobic and anaerobic conditions through glycolysis and metabolites, such as lactic acid and ATP, as a result of the Warburg effect. However, the transport of glucose into cells depends on protein transporters in the cell membrane. Therefore, this area has recently become a topic of interest for research on targeted cancer therapy. We found that miRNA-451 inhibits the phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway to modify the biological behavior of glioma cells. Inhibiting the PI3K/Akt pathway may prevent glucose-addicted cancer cells from performing glycolysis. Akt directly affects glycolysis by regulating the localization of the glucose transporter 1 (GLUT1). However, how miRNA-451 regulates glucose transporters on the cell membrane and affects the regulatory mechanisms of glucose metabolism in glioma cells remains unclear. Consequently, we predict and verify related gene protein interactions. By targeting CAB 39, miRNA-451 likely triggers the LKB1/AMPK/PI3K/AKT pathway, which regulates GLUT1, to inhibit the glucose metabolism of, reduce the energy supply to, and inhibit the proliferation and invasion of glioma cells. Our results suggest a new direction for the treatment of glioma.

背景与目标： : microrna在肿瘤的发展和进展中起重要作用。肿瘤生长与葡萄糖代谢密切相关。具体来说，由于Warburg效应，肿瘤细胞在有氧和厌氧条件下通过糖酵解和代谢产物 (例如乳酸和ATP) 产生能量 (ATP)。然而，葡萄糖向细胞的转运取决于细胞膜中的蛋白质转运蛋白。因此，该领域最近成为靶向癌症治疗研究的兴趣话题。我们发现miRNA-451抑制phosphatidylinositol-3激酶 (PI3K)/Akt信号通路来改变神经胶质瘤细胞的生物学行为。抑制PI3K/Akt途径可能会阻止葡萄糖成瘾的癌细胞进行糖酵解。Akt通过调节葡萄糖转运蛋白1 (GLUT1) 的定位直接影响糖酵解。然而，miRNA-451如何调节细胞膜上的葡萄糖转运蛋白并影响神经胶质瘤细胞中葡萄糖代谢的调节机制仍不清楚。因此，我们预测并验证了相关的基因蛋白相互作用。通过靶向CAB 39，miRNA-451可能会触发LKB1/AMPK/PI3K/AKT途径，该途径调节GLUT1，以抑制其葡萄糖代谢，减少能量供应并抑制神经胶质瘤细胞的增殖和侵袭。我们的结果为神经胶质瘤的治疗提供了新的方向。

BACKGROUND & AIMS: :miRNAs are key regulators that bind to target genes to suppress their gene expression level. The relations between miRNA-target genes enable users to derive co-expressed genes that may be involved in similar biological processes and functions in cells. We hypothesize that target genes of miRNAs are co-expressed, when they are regulated by multiple miRNAs. With the usage of these co-expressed genes, we can theoretically construct co-expression networks (GCNs) related to 152 diseases. In this study, we introduce ARNetMiT that utilize a hash based association rule algorithm in a novel way to infer the GCNs on miRNA-target genes data. We also present R package of ARNetMiT, which infers and visualizes GCNs of diseases that are selected by users. Our approach assumes miRNAs as transactions and target genes as their items. Support and confidence values are used to prune association rules on miRNA-target genes data to construct support based GCNs (sGCNs) along with support and confidence based GCNs (scGCNs). We use overlap analysis and the topological features for the performance analysis of GCNs. We also infer GCNs with popular GNI algorithms for comparison with the GCNs of ARNetMiT. Overlap analysis results show that ARNetMiT outperforms the compared GNI algorithms. We see that using high confidence values in scGCNs increase the ratio of the overlapped gene-gene interactions between the compared methods. According to the evaluation of the topological features of ARNetMiT based GCNs, the degrees of nodes have power-law distribution. The hub genes discovered by ARNetMiT based GCNs are consistent with the literature.

背景与目标： : mirna是与靶基因结合以抑制其基因表达水平的关键调节因子。miRNA-靶基因之间的关系使用户能够获得可能参与细胞中类似生物学过程和功能的共表达基因。我们假设mirna的靶基因被多个mirna调控时是共表达的。通过使用这些共表达基因，我们可以从理论上构建与152疾病相关的共表达网络 (GCNs)。在这项研究中，我们介绍了ARNetMiT，它以一种新颖的方式利用基于哈希的关联规则算法来推断miRNA靶基因数据上的GCNs。我们还介绍了ARNetMiT的R软件包，该软件包推断并可视化了用户选择的疾病的GCNs。我们的方法假设mirna作为交易，目标基因作为它们的项目。支持和置信度值用于修剪miRNA靶基因数据上的关联规则，以构建基于支持的GCNs (sGCNs) 以及基于支持和置信度的GCNs (scGCNs)。我们使用重叠分析和拓扑特征进行GCNs的性能分析。我们还使用流行的GNI算法推断GCNs，以与ARNetMiT的GCNs进行比较。重叠分析结果表明，ARNetMiT优于比较的GNI算法。我们看到，在scGCNs中使用高置信度值会增加比较方法之间重叠的基因-基因相互作用的比率。根据对基于ARNetMiT的GCNs的拓扑特征的评估，节点的度具有幂律分布。基于ARNetMiT的GCNs发现的hub基因与文献一致。

BACKGROUND & AIMS: :Osteosarcoma is the most common human primary malignant bone tumor in children and young adults. Sensitive and non-invasive biomarkers that can facilitate disease detection at early stage are highly desirable to improve survival rate and help to determine optimized treatment for osteosarcoma. The small non-coding RNAs, microRNAs (miRNAs), have recently been identified as critical regulators for various diseases including cancer and may represent a novel class of cancer biomarkers. In this study, we aimed to detect the potential of circulating miRNAs as biomarkers for osteosarcoma. Levels of six candidate miRNAs (miR-21, miR-199a-3p, miR-143, miR-34, miR-140, and miR-132) that were previously demonstrated to be regulated in osteosarcoma were examined in plasma of 40 osteosarcoma patients and 40 matched healthy controls by quantitative reverse-transcription polymerase chain reaction assays. The results showed that circulating levels of miR-21 were significantly higher in osteosarcoma patients than controls, while miR-199a-3p and miR-143 were decreased in osteosarcoma patients. We replicated the findings in an independent study of 40 osteosarcoma patients and 40 matched controls and confirmed the results. Receiver operating characteristics curve analysis of the combined populations demonstrated that the three-miRNA signature could discriminate cases from controls with an area under the curve of 0.953 (95 % CI 0.924-0.984). In addition, circulating miR-21 and miR-143 were correlated with both metastasis status and histological subtype of the patients, while miR-199a-3p only correlated with histological subtype. Our data suggest that altered levels of circulating miRNAs might have great potential to serve as novel, non-invasive biomarkers for osteosarcoma.

背景与目标： 骨肉瘤是儿童和年轻人中最常见的人类原发性恶性骨肿瘤。可以促进早期疾病检测的敏感和非侵入性生物标志物非常需要提高生存率并有助于确定骨肉瘤的最佳治疗方法。小的非编码rna，microrna (mirna)，最近已被确定为包括癌症在内的各种疾病的关键调节剂，并且可能代表一类新的癌症生物标志物。在这项研究中，我们旨在检测循环mirna作为骨肉瘤生物标志物的潜力。通过定量逆转录聚合酶链反应测定，在40名骨肉瘤患者和40名匹配的健康对照的血浆中检查了先前被证明在骨肉瘤中调控的六个候选mirna (miR-21，miR-199a-3p，miR-143，miR-34，miR-140和miR-132) 的水平。结果表明，骨肉瘤患者的miR-21循环水平明显高于对照组，而骨肉瘤患者的miR-199a-3p和miR-143水平降低。我们在一项针对40名骨肉瘤患者和40名匹配对照的独立研究中重复了这一发现，并证实了这一结果。组合种群的接收器工作特征曲线分析表明，三miRNA签名可以将病例与具有0.953曲线下面积的对照区分开 (95% CI 0.924-0.984)。此外，循环miR-21和miR-143与患者的转移状态和组织学亚型相关，而miR-199a-3p仅与组织学亚型相关。我们的数据表明，循环mirna水平的改变可能具有作为骨肉瘤的新型，非侵入性生物标志物的巨大潜力。

BACKGROUND & AIMS: :Although previous results showed that exogenous hydrogen (H2) alleviated aluminum (Al) toxicity, the detailed mechanism remains unclear. Here, we reported that the exposure of germinating rice seeds to Al triggered H2 production, followed by a decrease of GA/ABA ratio and seed germination inhibition. Compared to inert gas (argon), H2 pretreatment not only strengthened H2 production and alleviated Al-induced germination inhibition, but also partially reestablished the balance between GA and ABA. By contrast, a GA biosynthesis inhibitor paclobutrazol (PAC) could block the H2-alleviated germination inhibition. The expression of GA biosynthesis genes (GA20ox1 and GA20ox2) and ABA catabolism genes (ABA8ox1 and ABA8ox2), was also induced by H2. Above results indicated that GA/ABA might be partially involved in H2 responses. Subsequent results revealed that compared with Al alone, transcripts of miR398a and miR159a were decreased by H2, and expression levels of their target genes OsSOD2 and OsGAMYB were up-regulated. Whereas, miR528 and miR160a transcripts were increased differentially, and contrasting tendencies were observed in the changes of their target genes (OsAO and OsARF10). The transcripts of Al-tolerant gene OsSTAR1/OsSTAR2 and OsFRDL4 were up-regulated. Above results were consistent with the anti-oxidant defense, decreased Al accumulation, and enhanced citrate efflux. Together, our results provided insight into the mechanism underlying H2-triggered Al tolerance in plants.

背景与目标： : 尽管先前的结果表明外源氢 (H2) 减轻了铝 (Al) 的毒性，但详细的机理尚不清楚。在这里，我们报告了发芽的水稻种子暴露于Al会触发H2的产生，随后降低了GA/ABA比率并抑制了种子发芽。与惰性气体 (氩气) 相比，H2预处理不仅增强了H2的产生并减轻了Al诱导的发芽抑制，而且还部分恢复了GA和ABA之间的平衡。相比之下，GA生物合成抑制剂多效唑 (PAC) 可以阻断H2-alleviated发芽抑制。GA生物合成基因 (GA20ox1和GA20ox2) 和ABA分解代谢基因 (ABA8ox1和ABA8ox2) 的表达也被h2诱导。上述结果表明GA/ABA可能部分参与H2反应。随后的结果表明，与单独的Al相比，H2降低了miR398a和miR159a的转录本，并且其靶基因OsSOD2和OsGAMYB的表达水平上调。而miR528和miR160a转录本差异增加，并且在其靶基因 (OsAO和osaf10) 的变化中观察到相反的趋势。耐铝基因ossate1/ossate2和ossrdl4的转录本上调。上述结果与抗氧化防御，减少Al积累和增加柠檬酸盐外排一致。总之，我们的结果提供了对植物H2-triggered铝耐受性的潜在机制的见解。

BACKGROUND & AIMS: :Visceral leishmaniasis is characterized by mixed production of Th1/2 cytokines and the disease is established by an enhanced level of Th2 cytokine. CD4+ T cells are main cell type which produces Th1/2 cytokine in the host upon Leishmania infection. However, the regulatory mechanism for Th1/2 production is not well understood. In this study, we co-cultured mice CD4+ T cells with Leishmania donovani infected and uninfected macrophage for the identification of dysregulated miRNAs in CD4+ T cells by next-generation sequencing. Here, we identified 604 and 613 known miRNAs in CD4+ T cells in control and infected samples respectively and a total of only 503 miRNAs were common in both groups. The expression analysis revealed that 112 miRNAs were up and 96 were down-regulated in infected groups, compared to uninfected control. Nineteen up-regulated and 17 down-regulated miRNAs were statistically significant (p < 0.05), which were validated by qPCR. Further, using insilco approach, we identified the gene targets of significant miRNAs on the basis of CD4+ T cell biology. Eleven up-regulated miRNAs and 9 down-regulated miRNAs were associated with the cellular immune responses and Th1/2 dichotomy upon Leishmania donovani infection. The up-regulated miRNAs targeted transcription factors that promote differentiation of CD4+ T cells towards Th1 phenotype. While down-regulated miRNAs targeted the transcription factors that facilitate differentiation of CD4+ T cells towards Th2 populations. The GO and pathway enrichment analysis also showed that the identified miRNAs target the pathway and genes related to CD4+ T cell biology which plays important role in Leishmania donovani infection.

背景与目标： : 内脏利什曼病的特征是混合产生Th1/2细胞因子，并且该疾病是由Th2细胞因子水平升高引起的。CD4 + T细胞是利什曼原虫感染后在宿主中产生Th1/2细胞因子的主要细胞类型。然而，Th1/2生产的调节机制还没有很好的理解。在这项研究中，我们将小鼠CD4 T细胞与利什曼原虫多诺瓦尼感染和未感染的巨噬细胞共培养，以通过下一代测序鉴定CD4 T细胞中失调的mirna。在这里，我们分别在对照和感染样品中确定了CD4 + T细胞中的604和613已知的mirna，并且在两组中总共只有503个mirna是常见的。表达分析显示，与未感染对照组相比，感染组中有112个mirna升高，96个下调。19个上调和17个下调的mirna差异有统计学意义 (p  <  0.05)，qPCR验证。此外，使用insilco方法，我们基于CD4 T细胞生物学鉴定了重要mirna的基因靶标。11个上调的mirna和9个下调的mirna与利什曼原虫感染后的细胞免疫反应和Th1/2二分法相关。上调的miRNAs靶向转录因子，促进CD4 + T细胞向Th1表型分化。而下调的mirna靶向促进CD4 + T细胞向Th2群体分化的转录因子。GO和途径富集分析还表明，所鉴定的mirna靶向CD4 + T细胞生物学相关的途径和基因，在利什曼原虫感染中发挥重要作用。

BACKGROUND & AIMS: :RNA silencing refers to a series of nuclear and cytoplasmatic processes involved in the post-transcriptional regulation of gene expression or post-transcriptional gene silencing (PTGS), either by sequence-specific mRNA degradation or by translational arrest. The best characterized small RNAs are microRNAs (miRNAs), which predominantly perform gene silencing through post-transcriptional mechanisms. In this work we used bioinformatic approaches to identify the parasitic trematode Schistosoma mansoni sequences that are similar to enzymes involved in the post-transcriptional gene silencing mediated by miRNA pathway. We used amino acid sequences of well-known proteins involved in the miRNA pathway against S. mansoni genome and transcriptome databases identifying a total of 13 putative proteins in the parasite. In addition, the transcript levels of SmDicer1 and SmAgo2/3/4 were identified by qRT-PCR using cercariae, adult worms, eggs and in vitro cultivated schistosomula. Our results showed that the SmDicer1 and SmAgo2/3/4 are differentially expressed during schistosomula development, suggesting that the miRNA pathway is regulated at the transcript level and therefore may control gene expression during the life cycle of S. mansoni.

背景与目标： : RNA沉默是指通过序列特异性mRNA降解或通过翻译阻滞，参与基因表达的转录后调控或转录后基因沉默 (PTGS) 的一系列核和细胞质过程。表征最好的小rna是microRNAs (miRNAs)，它们主要通过转录后机制进行基因沉默。在这项工作中，我们使用生物信息学方法来鉴定曼氏血吸虫的寄生吸虫序列，这些序列与miRNA途径介导的转录后基因沉默中涉及的酶相似。我们使用了涉及针对曼氏链球菌基因组的miRNA途径的众所周知的蛋白质的氨基酸序列和转录组数据库，鉴定了该寄生虫中总共13种假定的蛋白质。此外，使用尾蚴，成虫，卵和体外培养的血吸虫，通过qRT-PCR鉴定SmDicer1和SmAgo2/3/4的转录水平。我们的结果表明SmDicer1和SmAgo2/3/4在血吸虫发育过程中差异表达，这表明miRNA途径在转录水平上受到调节，因此可能在曼氏链球菌的生命周期中控制基因表达。