scholarly journals Dysregulation of Principal Circulating miRNAs in Non-human Primates Following Ischemic Stroke

2021 ◽  
Vol 15 ◽  
Author(s):  
Jian Chen ◽  
Haiping Zhao ◽  
Yuyou Huang ◽  
Yuqian Li ◽  
Junfen Fan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Target Genes ◽  
Coiled Coil ◽  
Differentially Expressed ◽  
Research Progress ◽  
Protein Subunit ◽  
Chemokine Signaling ◽  
Plasma Microrna ◽  
Pathway Analyses

Despite the recent interest in plasma microRNA (miRNA) biomarkers in acute ischemic stroke patients, there is limited knowledge about the miRNAs directly related to stroke itself due to the multiple complications in patients, which has hindered the research progress of biomarkers and therapeutic targets of ischemic stroke. Therefore, in this study, we compared the differentially expressed miRNA profiles in the plasma of three rhesus monkeys pre- and post-cerebral ischemia. After cerebral ischemia, Rfam sequence category revealed increased ribosomic RNA (rRNA) and decreased transfer RNAs (tRNAs) in plasma. Of the 2049 miRNAs detected after cerebral ischemia, 36 were upregulated, and 76 were downregulated (fold change ≥2.0, P < 0.05). For example, mml-miR-191-5p, miR-421, miR-409-5p, and let-7g-5p were found to be significantly overexpressed, whereas mml-miR-128a-5p_R − 2, miR-431_R − 1, and let-7g-3p_1ss22CT were significantly downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these differentially expressed miRNAs were implicated in the regulation of ubiquitin-mediated proteolysis and signaling pathways in cancer, glioma, chronic myeloid leukemia, and chemokine signaling. miRNA clustering analysis showed that mml-let-7g-5p and let-7g-3p_1ss22CT, which share three target genes [RB1-inducible coiled-coil 1 (RB1CC1), G-protein subunit γ 5 (GNG5), and chemokine (C-X-C motif) receptor 4 (CXCR4)], belong to one cluster, were altered in opposite directions following ischemia. These data suggest that circulating mml-let-7g may serve as a therapeutic target for ischemic stroke.

scholarly journals Analysis of Circulating miRNA Profile in Plasma Samples of Glioblastoma Patients

2021 ◽  
Vol 22 (10) ◽  
pp. 5058
Author(s):  
Dóra Géczi ◽  
Bálint Nagy ◽  
Melinda Szilágyi ◽  
András Penyige ◽  
Álmos Klekner ◽  
...  
Keyword(s):  
Target Genes ◽  
Treatment Options ◽  
Enrichment Analysis ◽  
Specific Protein ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Plasma Samples ◽  
Functional Connections ◽  
Actual Application ◽  
Plasma Microrna

(1) Background: Glioblastoma multiforme (GBM) is among the most aggressive cancers with a poor prognosis. Treatment options are limited, clinicians lack efficient prognostic and predictive markers. Circulating miRNAs—besides being important regulators of cancer development—may have potential as diagnostic biomarkers of GBM. (2) Methods: In this study, profiling of 798 human miRNAs was performed on blood plasma samples from 6 healthy individuals and 6 patients with GBM, using a NanoString nCounter Analysis System. To validate our results, five miRNAs (hsa-miR-433-3p, hsa-miR-362-3p, hsa-miR-195-5p, hsa-miR-133a-3p, and hsa-miR-29a-3p) were randomly chosen for RT-qPCR detection. (3) Results: In all, 53 miRNAs were significantly differentially expressed in plasma samples of GBM patients when data were filtered for FC 1 and FDR 0.1. Target genes of the top 39 differentially expressed miRNAs were identified, and we carried out functional annotation and pathway enrichment analysis of target genes via GO and KEGG-based tools. General and cortex-specific protein–protein interaction networks were constructed from the target genes of top miRNAs to assess their functional connections. (4) Conclusions: We demonstrated that plasma microRNA profiles are promising diagnostic and prognostic molecular biomarkers that may find an actual application in the clinical practice of GBM, although more studies are needed to validate our results.

scholarly journals MiRNA biomarkers and potential critical genes associated with the prognosis of gastric cancer

2021 ◽  
Author(s):  
Zhou Chen ◽  
Hao Xu ◽  
Zhongtian Bai ◽  
Shi Dong ◽  
Jian Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Target Genes ◽  
Cox Model ◽  
Differential Expression Analysis ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Diagnosis And Prognosis ◽  
Kaplan Meier ◽  
Differentially Expressed Mirnas ◽  
Pathway Analyses

Abstract Background Dysregulated expression of miRNAs in gastric cancer (GC) is associated with tumor progression. MiRNA markers are important for the prognosis and therapeutic targeting of GC patients. Methods To detect differentially expressed miRNAs in GC from the TCGA database and predict their target genes. We downloaded RNA sequencing (RNA-seq), miRNA-seq and clinical data of GC from TCGA. Differential expression analysis of RNA-seq and miRNA-seq data was performed by R 3.6.1. MiRNAs associated with prognosis were evaluated with the Cox model, and differentially expressed miRNAs were assessed by Kaplan–Meier curve analysis. Risk factors were identified in the Cox model. Target genes of differentially expressed miRNAs were searched in three databases. GO enrichment and KEGG pathway analyses were used to evaluate the biological functions of these target genes.Results Five miRNAs (hsa-miR-135b-3p, hsa-miR-143-5p, hsa-miR-196b-3p, hsa-miR-942-3p, hsa-miR-9-3p) were related to survival. Eight target genes (AKAP12, AR, DZIP1, PCDHA11, PCDHA12, PI15, SH3BGRL and TMEM108) were closely correlated with patient overall survival (OS). Conclusion Differentially expressed miRNAs and their target genes have an important influence on the diagnosis and prognosis of GC and may be used as tumor biomarkers in further studies and as potential therapeutic targets.

The study of the significance and prognosis of the differential expressed miRNAs and their target genes associated with biological in colorectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15088-e15088
Author(s):  
Mingyun Wang ◽  
Mi Yang
Keyword(s):  
Colorectal Cancer ◽  
Target Genes ◽  
Biological Significance ◽  
Differentially Expressed ◽  
Prognostic Indicators ◽  
Receptor Interaction ◽  
Ppi Network ◽  
Prognostic Information ◽  
Chemokine Signaling ◽  
Chemokine Signaling Pathway

e15088 Background: MicroRNAs (miRNAs) have been related to prognostic indicators (such as stage and survival) in colorectal cancer. This study aimed to identify differentially expressed miRNAs and their target genes associated with biological significance and prognosis in colorectal cancer. Methods: The colorectal cancer, colorectal adenoma, and normal samples were obtained from the gene expression profile of GSE71187. A union of differentially expressed genes (DEGs) in the three groups was identified. The significantly different modules with highly interconnected DEGs were identified using weighted correlation network analysis (WGCNA) and were enriched to the KEGG pathway and GO function. Subsequently, the protein-protein interaction (PPI) network for DEGs in the module and the integrated regulatory network of miRNA-DEGs were constructed. In addition, the relationship of target DEGs and prognostic information was analyzed. Results: Three significantly different modules were identified, such as the brown, turquoise, and grey modules. The turquoise module including LTC4S, KLRK1, UNC5C, etc., which was mainly enriched to cell adhesion, cytokine−cytokine receptor interaction, and chemokine signaling pathway, inhibited the development of colorectal cancer. Subsequently, PPI network was constructed with the 678 DEGs in the three modules. Moreover, the miRNA-DEGs network was constructed with the 17 target DEGs (CXCR1, LTC4S, BTK, IGF1, etc.) and 14 miRNA (hsa-miR-335-5p, etc.). Finally, the overexpressed LTC4S was a good prognostic biomarker for colorectal cancer. Conclusions: The hsa-miR-335-5p might have potential prognosis value by targeting LTC4S and CXCR1 in colorectal cancer.

scholarly journals Identification of Novel LncRNA Biomarkers and Construction of LncRNA-Related Networks in Han Chinese Patients with Ischemic Stroke

2018 ◽  
Vol 50 (6) ◽  
pp. 2157-2175 ◽  
Author(s):  
Xiaojing Guo ◽  
Jialei Yang ◽  
Baoyun Liang ◽  
Tingting Shen ◽  
Yan Yan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Regulatory Network ◽  
Human Peripheral Blood ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Chinese Patients ◽  
Cerebral Disease ◽  
Significant Differential Expression ◽  
Qrt Pcr ◽  
Pathway Analyses

Background/Aims: Long non-coding RNAs (lncRNAs) are potential biomarkers of tumors, cardiac disease, and cerebral disease because of their interaction with coding RNAs. This work focused on ischemic stroke (IS) and aimed to identify novel lncRNA biomarkers and construct lncRNA-related networks in IS. Methods: Differentially expressed lncRNAs were identified using Arraystar Human LncRNA Microarray v4.0, and validated with qRT-PCR. A lncRNA–mRNA co-expression network and a lncRNA–miRNA–mRNA regulatory network were constructed. Functional and pathway analyses were then performed. Results: In total, 560 up-regulated and 690 down-regulated differentially expressed lncRNAs were found (P < 0.05, false discovery rate < 0.05, absolute fold change ≥ 2). qRT-PCR results confirmed that lncRNA-ENST00000568297, lncRNA-ENST00000568243, and lncRNA-NR_046084 exhibited significant differential expression between IS and controls (all P < 0.05). Areas under the curves (AUCs) for these lncRNAs were 0.733, 0.743, and 0.690, respectively, and the combined AUC was 0.843. A coding–noncoding co-expression (CNC) network was constructed based on Pearson’s correlation coefficient. A specific lncRNA–miRNA–mRNA regulatory network of ENST00000568297, ENST00000568243, and NR_046084 was also constructed. Functional annotation of the up- and down-regulated mRNAs was performed. Pathway analysis enriched IS-related pathways with mRNAs in the lncRNA–miRNA–mRNA regulatory network. Conclusion: LncRNA and mRNA expression profiles in human peripheral blood were altered after IS. ENST00000568297, ENST00000568243, and NR_046084 were identified as novel potential diagnostic biomarkers of IS. Analysis of the CNC network and lncRNA–miRNA–mRNA regulatory network suggested that lncRNAs may participate in IS pathophysiology by regulating pivotal miRNAs, mRNAs, or IS-related pathways.

scholarly journals Study on the Mechanism of Buyang Huanwu Decoction for the treatment of Ischemic Stroke Based on Network Pharmacology

2020 ◽  
Author(s):  
Kai Wang ◽  
Lu Lei ◽  
Jinyi Cao ◽  
Yi Qiao ◽  
Ruimin Liang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Clinical Practice ◽  
Cerebral Ischemia ◽  
Target Genes ◽  
Vascular Diseases ◽  
Network Pharmacology ◽  
Control Group ◽  
Active Components ◽  
Buyang Huanwu Decoction

Abstract Background: Buyang Huanwu Decoction (BYHWD) is one of the representative prescriptions for tonifying qi and promoting blood circulation. This formula has been widely used in Chinese clinical practice for treatment and prevention of ischemic cerebral vascular diseases. However, the mechanism and active compounds of BYHWD used in clinical practice for ischemic stroke are not well understood. The purpose of this study was to understand the potential active components of BYHWD and further explore its mechanism of improving ischemic stroke. Methods: This study was based on network pharmacology and bioinformatics analysis. The compounds of BYHWD were obtained from public databases. Oral bioavailability as well as drug-likeness were screened by using absorption, distribution, metabolism, and excretion (ADME) criteria. Then, components of BYHWD, candidate targets of each component and known therapeutic targets of ischemic cerebral were collected. A network of compound-target genes and compound-ischemic cerebral was established by means of network pharmacology data sources. The enrichment of key targets and pathways was analyzed by using string database and DAVID database. In addition, we verified three key targets predicted by western blot analysis (IL6, VEGFA and HIF1A). Results: Network pharmacology analysis results of BYHWD identified 7 herbs, 42 compounds and 79 target genes associated to cerebral ischemia. The 10 key compounds were baicalein, beta-carotene, Baicalin, kaempferol, luteolin, quercetin, hydroxysafflor yellow A, isorhamnetin, Bifendate, formononetin,Calycosin, AstragalosideIV, Stigmasterol, sitosterol, Z-ligustilide, Dihydrocapsaicin. Core genes in this network were IL6, TNF, VEGFA, HIF1A, MAPK1, MAPK3, JUN, STAT3, IL1B and IL10. And pathways TNF, IL-17, Apoptosis, PI3K-Akt, Toll-like receptor, MAPK, NF-kappa B and HIF-1 signaling pathway, etc. related to ischemic stroke were identified. In vitro experiments, The results showed that compared with the control group (no treatment), BYHWD could significantly inhibit the expression of IL6 and increased the expression of HIF1A and VEGFA. Conclusions: Network pharmacology analysis can reveal close interactions between multi-components and multi-targets, and enhance our understanding of the potential effects of BYHWD in cerebral ischemia.

scholarly journals MiRNAs expression profiling of rat ovaries displaying PCOS with insulin resistance

2020 ◽  
Vol 302 (5) ◽  
pp. 1205-1213
Author(s):  
Chunren Zhang ◽  
Chuyi Yu ◽  
Zengxian Lin ◽  
Haixia Pan ◽  
Kunyin Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Target Genes ◽  
Kegg Pathway ◽  
Polycystic Ovary ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Real Time Quantitative Pcr ◽  
Qrt Pcr ◽  
Differentially Expressed Mirnas ◽  
Pathway Analyses

Abstract Purpose The present study established microRNA (miRNA) expression profiles for rat ovaries displaying polycystic ovary syndrome (PCOS) with insulin resistance and explored the underlying biological functions of differentially expressed miRNAs. Methods A PCOS with insulin resistance rat model was created by administering letrozole and a high-fat diet. Total RNA was extracted from the ovaries of PCOS with insulin resistance rats and normal rats. Three ovaries from each group were used to identify differentially expressed miRNAs by deep sequencing. A hierarchical clustering heatmap and volcano plot were used to display the pattern of differentially expressed miRNAs. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to explore the potential target genes of the differentially expressed miRNAs and identify their putative biological function. Nine of the differentially expressed miRNAs were selected for validation by Real-time Quantitative PCR (qRT-PCR). Results A total of 58 differentially expressed miRNAs were identified in the rat ovaries exhibiting PCOS with insulin resistance compared with control ovaries, including 23 miRNAs that were upregulated and 35 miRNAs that were downregulated. GO and KEGG pathway analyses revealed that the predicted target genes were related to metabolic processes, cellular processes, and metabolic pathways. Furthermore, qRT-PCR confirmed that miR-3585-5p and miR-30-5p were significantly upregulated and miR-146-5p was downregulated in the ovaries of PCOS with insulin resistance rats compared with the controls. Conclusion These results indicate that differentially expressed miRNAs in rat ovaries may be involved in the pathophysiology of insulin resistance in PCOS. Our study may be beneficial in establishing miRNAs as novel diagnostic and therapeutic biomarkers for insulin resistance in PCOS.

scholarly journals Analysis of miRNA expression profiles in the liver of ClockΔ19 mutant mice

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8119
Author(s):  
Yanli Wang ◽  
Ke Lv ◽  
Mei Zhao ◽  
Hailong Chen ◽  
Guohua Ji ◽  
...  
Keyword(s):  
Liver Function ◽  
Signaling Pathway ◽  
Target Genes ◽  
Expression Profiles ◽  
Mapk Signaling ◽  
Mutant Mice ◽  
Differentially Expressed ◽  
Protein Protein Interaction ◽  
Mirnas Expression ◽  
Pathway Analyses

The circadian clock controls the physiological functions of many tissues including the liver via an autoregulatory transcriptional−translational feedback loop, of which CLOCK is a core positive component. In addition, many studies have indicated that microRNAs (miRNAs) regulate liver function. However, how CLOCK-regulated miRNAs are linked to liver function remains largely unknown. In this study, miRNAs expression profiles were performed in the liver of ClockΔ19 mutant mice. Compared to wild type mice, totals of 61 and 57 putative CLOCK-regulated miRNAs were differentially expressed (fold change absolute value ≥2) at zeitgeber time 2 and zeitgeber time 14, respectively. According to the pathway analyses, the target genes of differentially expressed miRNAs were mainly involved in pathways in cancer, the PI3K-Akt signaling pathway and the MAPK signaling pathway. Protein−protein interaction analyses revealed that the hub genes were primarily associated with pathway in cancer and circadian rhythms. Expression validation showed that while the expression levels of miR-195 and miR-340 were up-regulated, the rhythms of these two miRNAs were always maintained. The expression level of nr1d2 mRNA was down-regulated. We identified a number of prospective CLOCK-regulated miRNAs that play roles in the various physiological processes of the liver, providing a reference to better understanding the potential regulatory mechanisms in the liver.

Overexpression of miR-340-5p Inhibits Skin Fibroblast Proliferation by Targeting Kruppel-like Factor 2

2019 ◽  
Vol 20 (13) ◽  
pp. 1147-1154 ◽  
Author(s):  
Ling Chen ◽  
Qian Li ◽  
Xun Lu ◽  
Xiaohua Dong ◽  
Jingyun Li
Keyword(s):  
Gene Ontology ◽  
Skin Fibroblast ◽  
Kegg Pathway ◽  
Normal Skin ◽  
Skin Fibroblasts ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Fibroblast Proliferation ◽  
Pathway Analyses ◽  
Normal Skin Fibroblast

<P>Objective: MicroRNA (miR)-340-5p has been identified to play a key role in several cancers. However, the function of miR-340-5p in skin fibroblasts remains largely unknown. </P><P> Methods: Gain of function experiments were performed by infecting normal skin fibroblast cells with a lentivirus carrying 22-bp miR-340-5p. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8) assay. To uncover the mechanisms, mRNA-seq was used. Differentially expressed mRNAs were further determined by Gene Ontology and KEGG pathway analyses. The protein levels were analysed by Western blotting. A dual-luciferase reporter assay was used to detect the direct binding of miR-340-5p with the 3&#039;UTR of Kruppel-like factor 2 (KLF2). </P><P> Results: MiR-340-5p lentivirus infection suppressed normal skin fibroblast proliferation. The mRNAseq data revealed that 41 mRNAs were differentially expressed, including 22 upregulated and 19 downregulated transcripts in the miR-340-5p overexpression group compared with those in the control group. Gene Ontology and KEGG pathway analyses revealed that miR-340-5p overexpression correlated with the macromolecule biosynthetic process, cellular macromolecule biosynthetic process, membrane, and MAPK signalling pathway. Bioinformatics analysis and luciferase reporter assays showed that miR-340-5p binds to the 3&#039;UTR of KLF2. Forced expression of miR-340-5p decreased the expression of KLF2 in normal skin fibroblasts. Overexpression of KLF2 restored skin fibroblast proliferation in the miR-340-5p overexpression group. </P><P> Conclusion: This study demonstrates that miR-340-5p may suppress skin fibroblast proliferation, possibly through targeting KLF2. These findings could help us understand the function of miR-340-5p in skin fibroblasts. miR-340-5p could be a therapeutic target for preventing scarring.</P>

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.

Bioinformatics Analysis and Validation of Differentially Expressed MicroRNAs with Their Target Genes Involved in GLP-1RA Facilitated Osteogenesis

2020 ◽  
Vol 15 ◽  
Author(s):  
Na Wang ◽  
Yukun Li ◽  
Sijing Liu ◽  
Liu Gao ◽  
Chang Liu ◽  
...  
Keyword(s):  
High Throughput Sequencing ◽  
Target Genes ◽  
Bioinformatics Analysis ◽  
Differentially Expressed ◽  
Functional Study ◽  
Regulation Network ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled ◽  
Lower Expression

Background: Recent studies revealed that the hypoglycemic hormone, glucagon-like peptide-1 (GLP-1), acted as an important modulator in osteogenesis of bone marrow derived mesenchymal stem cells (BMSCs). Objectives: The aim of this study was to identify the specific microRNA (miRNA) using bioinformatics analysis and validate the presence of differentially expressed microRNAs with their target genes after GLP-1 receptor agonist (GLP-1RA) administration involved in ostogenesis of BMSCs. Methods: MiRNAs were extracted from BMSCs after 5 days’ treatment and sent for high-throughput sequencing for differentially expressed (DE) miRNAs analyses. Then the expression of the DE miRNAs verified by the real-time RT-PCR analyses. Target genes were predicted, and highly enriched GOs and KEGG pathway analysis were conducted using bioinformatics analysis. For the functional study, two of the target genes, SRY (sex determining region Y)-box 5 (SOX5) and G protein-coupled receptor 84 (GPR84), were identified. Results: A total of 5 miRNAs (miRNA-509-5p, miRNA-547-3p, miRNA-201-3p, miRNA-201-5p, and miRNA-novel-272-mature) were identified differentially expressed among groups. The expression of miRNA-novel-272-mature were decreased during the osteogenic differentiation of BMSCs, and GLP-1RA further decreased its expression. MiRNA-novel-272-mature might interact with its target mRNAs to enhance osteogenesis. The lower expression of miRNA-novel-272-mature led to an increase in SOX5 and a decrease in GPR84 mRNA expression, respectively. Conclusions: Taken together, these results provide further insights to the pharmacological properties of GLP-1RA and expand our knowledge on the role of miRNAs-mRNAs regulation network in BMSCs’ differentiation.

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