scholarly journals Plasma-Derived Exosomal hsa-miR-4488 and hsa-miR-1228-5p: Novel Biomarkers for Dermatomyositis-Associated Interstitial Lung Disease with Anti-Melanoma Differentiation-Associated Protein 5 Antibody-Positive Subset

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Danli Zhong ◽  
Chanyuan Wu ◽  
Dong Xu ◽  
Jingjing Bai ◽  
Qian Wang ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Target Genes ◽  
Homo Sapiens ◽  
Differentially Expressed ◽  
Transmission Electron ◽  
Exosomal Mirnas ◽  
Differentially Expressed Mirnas ◽  
Novel Biomarkers ◽  
And Gender

The present study is aimed at profiling circulating exosome-derived microRNAs (miRNAs/miRs) from patients with dermatomyositis (DM), in particular those complicated with interstitial lung disease (ILD) with anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive. Fifteen participants were enrolled, including five patients with DM complicated with ILDs prior to treatment with circulating anti-MDA5 antibody-positive status [DM-ILD-MDA5 Ab(+)], five DM patients without ILDs who were negative for 16 detectable myositis-specific antibodies [DM-nonILD-MSA16(-)], and five age- and gender-matched healthy donor controls (HCs). The characteristics of the exosomes extracted by Ribo™ Exosome Isolation Reagent were identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and flow cytometry. Differentially expressed miRNAs, determined by next-generation deep sequencing, were identified through the criteria of ∣ log 2   fold   change ∣ ≥ 1 and P < 0.01 . A total of 38 miRNAs were significantly upregulated in exosomes from patients with DM-ILD-MDA5 Ab(+) compared to those from HC, while 21 miRNAs were significantly downregulated. Compared to exosomes derived from patients with DM-nonILD-MSA16(-), 51 miRNAs were significantly upregulated and 33 miRNAs were significantly downregulated from patients with DM-ILD-MDA5 Ab(+). A total of 73 exosomal miRNAs were significantly differentially expressed between DM-nonILD-MSA16(-) and HC. In particular, two miRNAs, Homo sapiens- (hsa-) miR-4488 and hsa-miR-1228-5p, were common differentially expressed miRNAs among three comparisons. GO and KEGG analyses suggested that several pathways may contribute the pathogenesis of DM-ILD-MDA5 Ab(+) and DM-nonILD-MSA16(-), while PPI network analysis of hsa-miR-4488 and hsa-miR-1228-5p indicated that their predicted target genes, DExD-box helicase 39B and MDM2, may be involved in the mechanisms of DM-ILD-MDA5 Ab(+).

scholarly journals Identification of Potential ceRNA Network and Patterns of Immune Cell Infiltration in Systemic Sclerosis-Associated Interstitial Lung Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Qiuhong Wu ◽  
Yang Liu ◽  
Yan Xie ◽  
Shixiong Wei ◽  
Yi Liu
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Immune Cells ◽  
Regulatory Network ◽  
Target Genes ◽  
Immune Cell ◽  
Differentially Expressed ◽  
Immune Cell Infiltration ◽  
Overlapping Genes

PurposeSystemic sclerosis-associated interstitial lung disease (SSc-ILD) is one of the most severe complications of systemic sclerosis (SSc) and is the leading cause of SSc-related deaths. However, the precise pathogenesis of pulmonary fibrosis in SSc-ILD remains unknown. This study aimed to evaluate the competing endogenous RNA (ceRNA) regulatory network and immune cell infiltration patterns in SSc-ILD.MethodsOne microRNA (miRNA) and three messenger RNA (mRNA) microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. Then, the differentially expressed miRNAs (DEmiRs) and mRNAs (DEMs) between SSc-ILD patients and normal controls were identified, respectively, followed by the prediction of the target genes and target lncRNAs of DEmiRs. The overlapping genes between DEmiRs target genes and DEMs were identified as core mRNAs to construct the ceRNA network. In addition, the “Cell Type Identification by Estimating Relative Subsets of Known RNA Transcripts (CIBERSORT)” algorithm was used to analyze the composition of infiltrating immune cells in lung tissues of SSc-ILD patients and controls, and differentially expressed immune cells were recognized. The correlation between immune cells and core mRNAs was evaluated by Pearson correlation analysis.ResultsTotally, 42 SSc-ILD lung tissues and 18 normal lung tissues were included in this study. We identified 35 DEmiRs and 142 DEMs and predicted 1,265 target genes of DEmiRs. Then, 9 core mRNAs related to SSc-ILD were recognized, which were the overlapping genes between DEmiRs target genes and DEMs. Meanwhile, 9 DEmiRs related to core mRNAs were identified reversely, and their target lncRNAs were predicted. In total, 9 DEmiRs, 9 core mRNAs, and 51 predicted lncRNAs were integrated to construct the ceRNA regulatory network of SSc-ILD. In addition, 9 types of immune cells were differentially expressed in lung tissues between SSc-ILD patients and controls. Some core mRNAs, such as COL1A1, FOS, and EDN1, were positively or negatively correlated with the number of infiltrating immune cells.ConclusionThis is the first comprehensive study to construct the potential ceRNA regulatory network and analyze the composition of infiltrating immune cells in lung tissues of SSc-ILD patients, which improves our understanding of the pathogenesis of SSc-ILD.

scholarly journals Pancreatic Acinar Cells Employ miRNAs as Mediators of Intercellular Communication to Participate in the Regulation of Pancreatitis-Associated Macrophage Activation

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Yong Zhao ◽  
Hao Wang ◽  
Ming Lu ◽  
Xin Qiao ◽  
Bei Sun ◽  
...  
Keyword(s):  
Macrophage Activation ◽  
Target Genes ◽  
Culture Media ◽  
Mapk Pathway ◽  
Acinar Cells ◽  
Differentially Expressed ◽  
Pancreatic Acinar Cells ◽  
Supernatant Fraction ◽  
Exosomal Mirnas ◽  
Differentially Expressed Mirnas

Macrophage activation plays an important role in the inflammatory response in acute pancreatitis. In the present study, the activation of AR42J pancreatic acinar cells was induced by taurolithocholate treatment. The results showed that the culture medium from the activated AR42J cells significantly enhanced NFκB activation in the macrophages compared to that without taurolithocholate treatment. Additionally, the precipitates obtained from ultracentrifugation of the culture media that were rich in exosomes were markedly more potent in activating macrophages compared with the supernatant fraction lacking exosomes. The results indicated that the mediators carried by the exosomes played important roles in macrophage activation. Exosomal miRNAs were extracted and examined using microarrays. A total of 115 differentially expressed miRNAs were identified, and 30 showed upregulated expression, while 85 displayed downregulated expression. Target genes of the differentially expressed miRNAs were predicted using TargetScan, MiRanda, and PicTar software programs. The putative target genes were subjected to KEGG functional analysis. The functions of the target genes were primarily enriched in MAPK pathways. Specifically, the target genes regulated macrophage activation through the TRAF6-TAB2-TAK1-NIK/IKK-NFκB pathway. As the mediators of signal transduction, miRNAs and their predicted target mRNAs regulate every step in the MAPK pathway.

Bioinformatics Analysis Reveals Functions of MicroRNAs in Rice Under the Drought Stress

2021 ◽  
Vol 15 (8) ◽  
pp. 927-936 ◽  
Author(s):  
Yan Peng ◽  
Yuewu Liu ◽  
Xinbo Chen
Keyword(s):  
Drought Stress ◽  
Target Genes ◽  
Hot Spot ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Protein Protein Interaction ◽  
Promising Tool ◽  
Differentially Expressed Mirnas ◽  
Aba Biosynthesis

Background: Drought is one of the most damaging and widespread abiotic stresses that can severely limit the rice production. MicroRNAs (miRNAs) act as a promising tool for improving the drought tolerance of rice and have become a hot spot in recent years. Objective: In order to further extend the understanding of miRNAs, the functions of miRNAs in rice under drought stress are analyzed by bioinformatics. Method: In this study, we integrated miRNAs and genes transcriptome data of rice under the drought stress. Some bioinformatics methods were used to reveal the functions of miRNAs in rice under drought stress. These methods included target genes identification, differentially expressed miRNAs screening, enrichment analysis of DEGs, network constructions for miRNA-target and target-target proteins interaction. Results: (1) A total of 229 miRNAs with differential expression in rice under the drought stress, corresponding to 73 rice miRNAs families, were identified. (2) 1035 differentially expressed genes (DEGs) were identified, which included 357 up-regulated genes, 542 down-regulated genes and 136 up/down-regulated genes. (3) The network of regulatory relationships between 73 rice miRNAs families and 1035 DEGs was constructed. (4) 25 UP_KEYWORDS terms of DEGs, 125 GO terms and 7 pathways were obtained. (5) The protein-protein interaction network of 1035 DEGs was constructed. Conclusion: (1) MiRNA-regulated targets in rice might mainly involve in a series of basic biological processes and pathways under drought conditions. (2) MiRNAs in rice might play critical roles in Lignin degradation and ABA biosynthesis. (3) MiRNAs in rice might play an important role in drought signal perceiving and transduction.

Abstract WMP30: Circulating MicroRNAs as Potential Novel Diagnostic Biomarkers for Ruptured Intracranial Aneurysm

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Zhang Xin ◽  
Liu L Ping
Keyword(s):  
Intracranial Aneurysm ◽  
Target Genes ◽  
Bioinformatic Analysis ◽  
Aneurysm Rupture ◽  
Pathological Process ◽  
Differentially Expressed ◽  
Diagnostic Biomarkers ◽  
Ruptured Intracranial Aneurysm ◽  
Novel Biomarkers ◽  
Aneurysm Development

Background and Objective: MicroRNAs have been shown to regulate in several pathological process of intracranial aneurysms. The study aimed to estimate whether miRNAs have the potential to become novel biomarkers for intracranial aneurysm rupture. Materials and methods Forty-five ruptured intracranial aneurysm patients were enrolled according to the inclusion criteria, meanwhile thirty-five healthy individuals were recruited in this study. Differentially expressed plasma miRNA profiles were screened in five pairs of patients and controls in microarray study. Then validation was performed in the rest of the objects using quantitative real-time PCR assays. Results: Fourteen significantly changed miRNAs were screened out from patients with aneurysms compared with healthy controls. More than three thousand target genes related to these disregulated miRNAs were found and bioinformatic analysis revealed that these miRNA were involved in intracranial aneurysm development and rupture. Ultimately four miRNAs from screening profile and one supplementary miRNA were demonstrated to be significantly altered. Conclusion: We demonstrated that several miRNAs were differentially expressed among ruptured aneurysm patients and healthy participants, and plasma miRNAs may be novel diagnostic biomarkers in intracranial aneurysm rupture.

scholarly journals MicroRNA sequence analysis identifies microRNAs associated with peri-implantitis in dogs

2017 ◽  
Vol 37 (5) ◽  
Author(s):  
Xiaolin Wu ◽  
Xipeng Chen ◽  
Wenxiang Mi ◽  
Tingting Wu ◽  
Qinhua Gu ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Target Genes ◽  
Alveolar Bone ◽  
Biological Effects ◽  
Bone Destruction ◽  
Mapk Signaling ◽  
Differentially Expressed ◽  
Mitogen Activated Protein Kinase ◽  
Mirna Sequence ◽  
Differentially Expressed Mirnas

Peri-implantitis, which is characterized by dense inflammatory infiltrates and increased osteoclast activity, can lead to alveolar bone destruction and implantation failure. miRNAs participate in the regulation of various inflammatory diseases, such as periodontitis and osteoporosis. Therefore, the present study aimed to investigate the differential expression of miRNAs in canine peri-implantitis and to explore the functions of their target genes. An miRNA sequence analysis was used to identify differentially expressed miRNAs in peri-implantitis. Under the criteria of a fold-change >1.5 and P<0.01, 8 up-regulated and 30 down-regulated miRNAs were selected for predictions of target genes and their biological functions. Based on the results of Gene Ontology (GO) and KEGG pathway analyses, these miRNAs may fine-tune the inflammatory process in peri-implantitis through an intricate mechanism. The results of quantitative real-time PCR (qRT-PCR) revealed that let-7g, miR-27a, and miR-145 may play important roles in peri-implantitis and are worth further investigation. The results of the present study provide insights into the potential biological effects of the differentially expressed miRNAs, and specific enrichment of target genes involved in the mitogen-activated protein kinase (MAPK) signaling pathway was observed. These findings highlight the intricate and specific roles of miRNAs in inflammation and osteoclastogenesis, both of which are key aspects of peri-implantitis, and thus may contribute to future investigations of the etiology, underlying mechanism, and treatment of peri-implantitis.

scholarly journals Peripheral Circulating Exosomal miRNAs Potentially Contribute to the Regulation of Molecular Signaling Networks in Aging

2020 ◽  
Vol 21 (6) ◽  
pp. 1908 ◽  
Author(s):  
Hongxia Zhang ◽  
Kunlin Jin
Keyword(s):  
Target Genes ◽  
Differentially Expressed ◽  
Molecular Signaling ◽  
Slow Development ◽  
Exosomal Mirnas ◽  
Pathways Analysis ◽  
Old Rats ◽  
Underlying Mechanisms ◽  
Signaling Components ◽  
Serum Exosomes

People are living longer than ever. Consequently, they have a greater chance for developing a functional impairment or aging-related disease, such as a neurodegenerative disease, later in life. Thus, it is important to identify and understand mechanisms underlying aging as well as the potential for rejuvenation. Therefore, we used next-generation sequencing to identify differentially expressed microRNAs (miRNAs) in serum exosomes isolated from young (three-month-old) and old (22-month-old) rats and then used bioinformatics to explore candidate genes and aging-related pathways. We identified 2844 mRNAs and 68 miRNAs that were differentially expressed with age. TargetScan revealed that 19 of these miRNAs are predicated to target the 766 mRNAs. Pathways analysis revealed signaling components targeted by these miRNAs: mTOR, AMPK, eNOS, IGF, PTEN, p53, integrins, and growth hormone. In addition, the most frequently predicted target genes regulated by these miRNAs were EIF4EBP1, insulin receptor, PDK1, PTEN, paxillin, and IGF-1 receptor. These signaling pathways and target genes may play critical roles in regulating aging and lifespan, thereby validating our analysis. Understanding the causes of aging and the underlying mechanisms may lead to interventions that could reverse certain aging processes and slow development of aging-related diseases.

scholarly journals Identification of New miRNA-mRNA Networks in the Development of Non-syndromic Cleft Lip With or Without Cleft Palate

2021 ◽  
Vol 9 ◽  
Author(s):  
Chengyi Fu ◽  
Shu Lou ◽  
Guirong Zhu ◽  
Liwen Fan ◽  
Xin Yu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cleft Palate ◽  
Negative Correlation ◽  
Cell Apoptosis ◽  
Cleft Lip ◽  
Target Genes ◽  
Craniofacial Development ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas

Objective: To identify new microRNA (miRNA)-mRNA networks in non-syndromic cleft lip with or without cleft palate (NSCL/P).Materials and Methods: Overlapping differentially expressed miRNAs (DEMs) were selected from cleft palate patients (GSE47939) and murine embryonic orofacial tissues (GSE20880). Next, the target genes of DEMs were predicted by Targetscan, miRDB, and FUNRICH, and further filtered through differentially expressed genes (DEGs) from NSCL/P patients and controls (GSE42589), MGI, MalaCards, and DECIPHER databases. The results were then confirmed by in vitro experiments. NSCL/P lip tissues were obtained to explore the expression of miRNAs and their target genes.Results: Let-7c-5p and miR-193a-3p were identified as DEMs, and their overexpression inhibited cell proliferation and promoted cell apoptosis. PIGA and TGFB2 were confirmed as targets of let-7c-5p and miR-193a-3p, respectively, and were involved in craniofacial development in mice. Negative correlation between miRNA and mRNA expression was detected in the NSCL/P lip tissues. They were also associated with the occurrence of NSCL/P based on the MGI, MalaCards, and DECIPHER databases.Conclusions: Let-7c-5p-PIGA and miR-193a-3p-TGFB2 networks may be involved in the development of NSCL/P.

scholarly journals Identification of cold stress responsive microRNAs in cold tolerant and susceptible Hemerocallis fulva by high throughput sequencing

2020 ◽  
Author(s):  
Changbing Huang ◽  
Chun Jiang ◽  
limin Jin ◽  
Huanchao Zhang
Keyword(s):  
Low Temperature ◽  
Cold Stress ◽  
Cold Tolerance ◽  
Temperature Stress ◽  
Stress Responses ◽  
Target Genes ◽  
Low Temperature Stress ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas ◽  
Cold Tolerant

Abstract Background:Hemerocallis fulva is a perennial herb belonging to Hemerocallis of Hemerocallis. Because of the large and bright colors, it is often used as a garden ornamental plant. But most varieties of H. fulva on the market will wither in winter, which will affect their beauty. It is very important to study the effect of low temperature stress on the physiological indexes of H. fulva and understand the cold tolerance of different H. fulva. MiRNA is a kind of endogenous non coding small molecular RNA with length of 21-24nt. It mainly inhibits protein translation by cutting target genes, and plays an important role in the development of organisms, gene expression and biological stress. Low temperature is the main abiotic stress affecting the production of H. fulva in China, which hinders the growth and development of plants. A comprehensive understanding of the expression pattern of microRNA in H. fulva under low temperature stress can improve our understanding of microRNA mediated stress response. Although there are many studies on miRNAs of various plants under cold stress at home and abroad, there are few studies on miRNAs related to cold stress of H. fulva. It is of great significance to explore the cold stress resistant gene resources of H. fulva, especially the identification and functional research of miRNA closely related to cold stress, for the breeding of excellent H. fulva.Results A total of 5619 cold-responsive miRNAs, 315 putative novel and 5 304 conserved miRNAs, were identified from the leaves and roots of two different varieties ‘Jinyan’ (cold-tolerant) and ‘Lucretius ’ (cold-sensitive), which were stressed under -4 oC for 24 h. Twelve conserved and three novel miRNAs (novel-miR10, novel-miR19 and novel-miR48) were differentially expressed in leaves of ‘Jinyan’ under cold stress. Novel-miR19, novel-miR29 and novel-miR30 were up-regulated in roots of ‘Jinyan’ under cold stress. Thirteen and two conserved miRNAs were deferentially expressed in leaves and roots of ‘Lucretius’ after cold stress. The deferentially expressed miRNAs between two cultivars under cold stress include novel miRNAs and the members of the miR156, miR166 and miR319 families. A total of 6 598 target genes for 6 516 known miRNAs and 82 novel miRNAs were predicted by bioinformatic analysis, mainly involved in metabolic processes and stress responses. Ten differentially expressed miRNAs and predicted target genes were confirmed by quantitative reverse transcription PCR(q-PCR), and the expressional changes of target genes were negatively correlated to differentially expressed miRNAs. Our data indicated that some candidate miRNAs (e.g., miR156a-3-p, miR319a, and novel-miR19) may play important roles in plant response to cold stress.Conclusions Our study indicates that some putative target genes and miRNA mediated metabolic processes and stress responses are significant to cold tolerance in H. fulva.

scholarly journals Construction and validation of a novel prognostic signature of microRNAs in lung adenocarcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10470
Author(s):  
Wanzhen Li ◽  
Shiqing Liu ◽  
Shihong Su ◽  
Yang Chen ◽  
Gengyun Sun
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Prognostic Value ◽  
Target Genes ◽  
Predictive Accuracy ◽  
Differentially Expressed ◽  
Prognostic Signature ◽  
Tissue Samples ◽  
Gene Set ◽  
Differentially Expressed Mirnas

MicroRNA (miRNA, miR) has been reported to be highly implicated in a wide range of biological processes in lung cancer (LC), and identification of differentially expressed miRNAs between normal and LC samples has been widely used in the discovery of prognostic factors for overall survival (OS) and response to therapy. The present study was designed to develop and evaluate a miRNA-based signature with prognostic value for the OS of lung adenocarcinoma (LUAD), a common histologic subtype of LC. In brief, the miRNA expression profiles and clinicopathological factors of 499 LUAD patients were collected from The Cancer Genome Atlas (TCGA) database. Kaplan–Meier (K-M) survival analysis showed significant correlations between differentially expressed miRNAs and LUAD survival outcomes. Afterward, 1,000 resample LUAD training matrices based on the training set was applied to identify the potential prognostic miRNAs. The least absolute shrinkage and selection operator (LASSO) cox regression analysis was used to constructed a six-miRNA based prognostic signature for LUAD patients. Samples with different risk scores displayed distinct OS in K-M analysis, indicating considerable predictive accuracy of this signature in both training and validation sets. Furthermore, time-dependent receiver operating characteristic (ROC) analysis demonstrated the nomogram achieved higher predictive accuracy than any other clinical variables after incorporating the clinical information (age, sex, stage, and recurrence). In the stratification analysis, the prognostic value of this classifier in LUAD patients was validated to be independent of other clinicopathological variables, such as age, gender, tumor recurrence, and early stage. Gene set annotation analyses were also conducted through the Hallmark gene set and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, indicating target genes of the six miRNAs were positively related to various molecular pathways of cancer, such as hallmark UV response, Wnt signaling pathway and mTOR signaling pathway. In addition, fresh cancer tissue samples and matched adjacent tissue samples from 12 LUAD patients were collected to verify the expression of miR-582’s target genes in the model, further revealing the potential relationship between SOX9, RASA1, CEP55, MAP4K4 and LUAD tumorigenesis, and validating the predictive value of the model. Taken together, the present study identified a robust signature for the OS prediction of LUAD patients, which could potentially aid in the individualized selection of therapeutic approaches for LUAD patients.

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