scholarly journals miRNA and miRNA target genes in intervention effect of Zhuyu pill on cholestatic rat model

2021 ◽  
pp. 114709
Author(s):  
Han Yu ◽  
Chao Liu ◽  
Jianfei Wang ◽  
Jun Han ◽  
Fenghua Zhang ◽  
...  
Keyword(s):  
Rat Model ◽  
Mirna Target ◽  
Target Genes ◽  
Intervention Effect

scholarly journals Regulatory Network Analysis in Estradiol-Treated Human Endothelial Cells

2021 ◽  
Vol 22 (15) ◽  
pp. 8193
Author(s):  
Daniel Pérez-Cremades ◽  
Ana B. Paes ◽  
Xavier Vidal-Gómez ◽  
Ana Mompeón ◽  
Carlos Hermenegildo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Regulatory Network ◽  
Mirna Target ◽  
Target Genes ◽  
Functional Characterization ◽  
Human Endothelial Cells ◽  
Mrna Targets ◽  
Canonical Pathways

Background/Aims: Estrogen has been reported to have beneficial effects on vascular biology through direct actions on endothelium. Together with transcription factors, miRNAs are the major drivers of gene expression and signaling networks. The objective of this study was to identify a comprehensive regulatory network (miRNA-transcription factor-downstream genes) that controls the transcriptomic changes observed in endothelial cells exposed to estradiol. Methods: miRNA/mRNA interactions were assembled using our previous microarray data of human umbilical vein endothelial cells (HUVEC) treated with 17β-estradiol (E2) (1 nmol/L, 24 h). miRNA–mRNA pairings and their associated canonical pathways were determined using Ingenuity Pathway Analysis software. Transcription factors were identified among the miRNA-regulated genes. Transcription factor downstream target genes were predicted by consensus transcription factor binding sites in the promoter region of E2-regulated genes by using JASPAR and TRANSFAC tools in Enrichr software. Results: miRNA–target pairings were filtered by using differentially expressed miRNAs and mRNAs characterized by a regulatory relationship according to miRNA target prediction databases. The analysis identified 588 miRNA–target interactions between 102 miRNAs and 588 targets. Specifically, 63 upregulated miRNAs interacted with 295 downregulated targets, while 39 downregulated miRNAs were paired with 293 upregulated mRNA targets. Functional characterization of miRNA/mRNA association analysis highlighted hypoxia signaling, integrin, ephrin receptor signaling and regulation of actin-based motility by Rho among the canonical pathways regulated by E2 in HUVEC. Transcription factors and downstream genes analysis revealed eight networks, including those mediated by JUN and REPIN1, which are associated with cadherin binding and cell adhesion molecule binding pathways. Conclusion: This study identifies regulatory networks obtained by integrative microarray analysis and provides additional insights into the way estradiol could regulate endothelial function in human endothelial cells.

scholarly journals Identification and Classification of Hubs in microRNA Target Gene Networks in Human Neural Stem/Progenitor Cells following Japanese Encephalitis Virus Infection

mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Sriparna Mukherjee ◽  
Irshad Akbar ◽  
Reshma Bhagat ◽  
Bibhabasu Hazra ◽  
Arindam Bhattacharyya ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Gene Networks ◽  
Mirna Target ◽  
Target Gene ◽  
Target Genes ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Neural Stem Progenitor Cells

ABSTRACT RNA viruses are known to modulate host microRNA (miRNA) machinery for their own benefit. Japanese encephalitis virus (JEV), a neurotropic RNA virus, has been reported to manipulate several miRNAs in neurons or microglia. However, no report indicates a complete sketch of the miRNA profile of neural stem/progenitor cells (NSPCs), hence the focus of our current study. We used an miRNA array of 84 miRNAs in uninfected and JEV-infected human neuronal progenitor cells and primary neural precursor cells isolated from aborted fetuses. Severalfold downregulation of hsa-miR-9-5p, hsa-miR-22-3p, hsa-miR-124-3p, and hsa-miR-132-3p was found postinfection in both of the cell types compared to the uninfected cells. Subsequently, we screened for the target genes of these miRNAs and looked for the biological pathways that were significantly regulated by the genes. The target genes involved in two or more pathways were sorted out. Protein-protein interaction (PPI) networks of the miRNA target genes were formed based on their interaction patterns. A binary adjacency matrix for each gene network was prepared. Different modules or communities were identified in those networks by community detection algorithms. Mathematically, we identified the hub genes by analyzing their degree centrality and participation coefficient in the network. The hub genes were classified as either provincial (P < 0.4) or connector (P > 0.4) hubs. We validated the expression of hub genes in both cell line and primary cells through qRT-PCR after JEV infection and respective miR mimic transfection. Taken together, our findings highlight the importance of specific target gene networks of miRNAs affected by JEV infection in NSPCs. IMPORTANCE JEV damages the neural stem/progenitor cell population of the mammalian brain. However, JEV-induced alteration in the miRNA expression pattern of the cell population remains an open question, hence warranting our present study. In this study, we specifically address the downregulation of four miRNAs, and we prepared a protein-protein interaction network of miRNA target genes. We identified two types of hub genes in the PPI network, namely, connector hubs and provincial hubs. These two types of miRNA target hub genes critically influence the participation strength in the networks and thereby significantly impact up- and downregulation in several key biological pathways. Computational analysis of the PPI networks identifies key protein interactions and hubs in those modules, which opens up the possibility of precise identification and classification of host factors for viral infection in NSPCs.

scholarly journals Prediction of human miRNA target genes using computationally reconstructed ancestral mammalian sequences

2016 ◽  
Vol 45 (2) ◽  
pp. 556-566 ◽  
Author(s):  
Mickael Leclercq ◽  
Abdoulaye Baniré Diallo ◽  
Mathieu Blanchette
Keyword(s):  
Mirna Target ◽  
Target Genes

scholarly journals Global Analysis of the Genetic Variations in miRNA-Targeted Sites and Their Correlations With Agronomic Traits in Rapeseed

2021 ◽  
Vol 12 ◽  
Author(s):  
Pengfei Xu ◽  
Yantao Zhu ◽  
Yanfeng Zhang ◽  
Jianxia Jiang ◽  
Liyong Yang ◽  
...  
Keyword(s):  
Mirna Target ◽  
Target Genes ◽  
Rare Variants ◽  
Agronomic Traits ◽  
Global Analysis ◽  
Variant Calling ◽  
Genetic Variations ◽  
Nucleotide Polymorphisms ◽  
A Genome ◽  
Target Sites

MicroRNAs (miRNAs) and their target genes play vital roles in crops. However, the genetic variations in miRNA-targeted sites that affect miRNA cleavage efficiency and their correlations with agronomic traits in crops remain unexplored. On the basis of a genome-wide DNA re-sequencing of 210 elite rapeseed (Brassica napus) accessions, we identified the single nucleotide polymorphisms (SNPs) and insertions/deletions (INDELs) in miRNA-targeted sites complementary to miRNAs. Variant calling revealed 7.14 million SNPs and 2.89 million INDELs throughout the genomes of 210 rapeseed accessions. Furthermore, we detected 330 SNPs and 79 INDELs in 357 miRNA target sites, of which 33.50% were rare variants. We also analyzed the correlation between the genetic variations in miRNA target sites and 12 rapeseed agronomic traits. Eleven SNPs in miRNA target sites were significantly correlated with phenotypes in three consecutive years. More specifically, three correlated SNPs within the miRNA-binding regions of BnSPL9-3, BnSPL13-2, and BnCUC1-2 were in the loci associated with the branch angle, seed weight, and silique number, respectively; expression profiling suggested that the variation at these 3 miRNA target sites significantly affected the expression level of the corresponding target genes. Taken together, the results of this study provide researchers and breeders with a global view of the genetic variations in miRNA-targeted sites in rapeseed and reveal the potential effects of these genetic variations on elite agronomic traits.

scholarly journals The Computational Analysis Conducted on miRNA Target Sites in Association with SNPs at 3’UTR of ADHD-implicated Genes

2020 ◽  
Vol 20 (1) ◽  
pp. 58-75
Author(s):  
Adel Abdi ◽  
Mina Zafarpiran ◽  
Zeinab S. Farsani
Keyword(s):  
Binding Sites ◽  
Mirna Target ◽  
Target Genes ◽  
Target Prediction ◽  
Functional Verification ◽  
Candidate Snps ◽  
Epigenetic Factors ◽  
Hyperactivity Disorder ◽  
Mrna Gene ◽  
Recognition Elements

Background: Attention-deficit/hyperactivity disorder (ADHD) is a frequent chronic neuropsychiatric disorder in which different factors including environmental, genetic, and epigenetic factors play an important role in its pathogenesis. One of the effective epigenetic factors is recognized as MicroRNAs (miRNAs). On the other hand, it has been indicated that the single nucleotide polymorphism (SNPs) present within 3'UTR (3' untranslated region) of mRNAs can influence the regulation of miRNA-mediated gene and susceptibility to a diversity of human diseases. Methods: The purpose of this study was to analyze the SNPs within the 3'UTR of miRNA target genes associated with ADHD. 3'UTR genetic variants were identified in all genes associated with ADHD using DisGeNET, dbGaP, Ovid, DAVID, Web of knowledge, and SNPs databases. miRNA's target prediction databases were applied in order to predict the miRNA binding sites. 124 SNPs with MAF>0.05 were identified located in the binding site of the miRNA of 35 genes amongst 51 genes associated with ADHD. Results: Bioinformatics analysis predicted 81 MRE (miRNA recognition elements)-creating SNPs, 101 MRE-breaking SNPs, 61 MRE-enhancing SNPs, and finally predicted 41 MREdecreasing SNPs in the 3'UTR of ADHD-implicated genes. These candidate SNPs within these genes miRNA binding sites can alter the miRNAs binding, and consequently, lead to mRNA gene regulation. Conclusion: Therefore, these miRNA and MRE-SNPs may play important roles in ADHD, and because of that, they would be valuable for further investigation in the field of functional verification.

scholarly journals Circulating miRNAs as a Predictive Biomarker of the Progression from Prediabetes to Diabetes: Outcomes of a 5-Year Prospective Observational Study

2020 ◽  
Vol 9 (7) ◽  
pp. 2184 ◽  
Author(s):  
Iwona Sidorkiewicz ◽  
Magdalena Niemira ◽  
Katarzyna Maliszewska ◽  
Anna Erol ◽  
Agnieszka Bielska ◽  
...  
Keyword(s):  
Pathway Analysis ◽  
Mirna Target ◽  
Target Genes ◽  
Quantitative Polymerase Chain Reaction ◽  
Area Under The Curve ◽  
Predictive Biomarkers ◽  
Predictive Biomarker ◽  
Circulating Mirnas ◽  
Serum Samples ◽  
Roc Curve Analysis

Due to a global increase in the prevalence of type 2 diabetes mellitus (T2DM), there is an urgent need for early identification of prediabetes, as these people have the highest risk of developing diabetes. Circulating miRNAs have shown potential as progression biomarkers in other diseases. This study aimed to conduct a baseline comparison of serum-circulating miRNAs in prediabetic individuals, with the distinction between those who later progressed to T2DM and those who did not. The expression levels of 798 miRNAs using NanoString technology were examined. Spearman correlation, receiver operating characteristic (ROC) curve analysis, and logistic regression modeling were performed. Gene ontology (GO) and canonical pathway analysis were used to explore the biological functions of the miRNA target genes. The study revealed that three miRNAs were upregulated in the serum samples of patients who later progressed to T2DM. Pathway analysis showed that the miRNA target genes were mainly significantly enriched in neuronal NO synthase (nNOS) signaling in neurons, amyloid processing, and hepatic cholestasis. ROC analysis demonstrated that miR-491-5p, miR-1307-3p, and miR-298 can be introduced as a diagnostic tool for the prediction of T2DM (area under the curve (AUC) = 94.0%, 88.0%, and 84.0%, respectively). Validation by real-time quantitative polymerase chain reaction (qRT-PCR) confirmed our findings. The results suggest that circulating miRNAs can potentially be used as predictive biomarkers of T2DM in prediabetic patients.

scholarly journals Identifying metastasis-initiating miRNA-target regulations of colorectal cancer from expressional changes in primary tumors

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jongmin Lee ◽  
Hye Kyung Hong ◽  
Sheng-Bin Peng ◽  
Tae Won Kim ◽  
Woo Yong Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Mirna Target ◽  
Target Genes ◽  
Expression Profiles ◽  
Statistical Significance ◽  
Primary Tumors ◽  
Significant Difference

Abstract Colorectal cancer (CRC) is prevalent with high mortality, with liver metastasis contributing as a major factor that worsens the survival of patients. The roles of miRNAs in CRC have been elucidated, subsequent to recent studies that suggest the involvement of miRNAs in cancer biology. In this study, we compare the miRNA and gene expression profiles of primary tumors between two groups of patients (with and without liver metastasis) to identify the metastasis-initiating microRNA-target gene regulations. Analysis from 33 patients with metastasis and 14 patients without metastasis revealed that 17 miRNAs and their 198 predicted target genes are differentially expressed, where the target genes showed association with cancer progression and metastasis with statistical significance. In order to evaluate the clinical implications of the findings, we classified CRC patients of independent data into two groups based on the identified miRNA-target regulations, where one group was closer to primary tumors with metastasis than the other group. The comparison of survival showed statistically significant difference, thereby implying the roles of the identified miRNA-target regulations in cancer progression and metastasis. The identification of metastasis-initiating miRNA-target regulations in this study will lead to better understanding of the roles of miRNAs in CRC progression.

Astragaloside IV ameliorates preeclampsia-induced oxidative stress through the Nrf2/HO-1 pathway in a rat model

2020 ◽  
Vol 319 (5) ◽  
pp. E904-E911 ◽  
Author(s):  
Shuangyan Yang ◽  
Ruixue Zhang ◽  
Baoheng Xing ◽  
Ling Zhou ◽  
Peipei Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Target Genes ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Astragaloside Iv ◽  
Pregnant Rats ◽  
Beneficial Effects ◽  
Antioxidative Effects ◽  
Protein Serum

Preeclampsia (PE) can cause serious health problems for pregnant women and their infants. Astragaloside IV has been shown to exert cardioprotective, anti-inflammatory, and antioxidative effects on various disorders. We aimed to study the effects of Astragaloside IV on PE symptoms using an NG-nitro-l-arginine methyl ester (l-NAME)-induced rat model of PE. The pregnant rats’ physiological features, including blood pressure, urine protein, serum soluble fms-like tyrosine kinase- 1 ( sFlt - 1)/placental growth factor (PlGF) ratio, and weight of placenta, as well as the weight, length, and survival of pups, were documented. The expression levels of target genes were analyzed by Western blot and qRT-PCR assays. The levels of target secreted proteins were determined by ELISA. We demonstrated that the administration of Astragaloside IV might exert a multitude of beneficial effects on attenuated PE symptoms in a rat model of PE. We further revealed that the effects of Astragaloside IV on PE rats were achieved, at least partially, through elimination of oxidative stress and stimulation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. Our study indicated that Astragaloside IV may serve as a promising candidate for the development of new therapeutic methods for patients with PE.

scholarly journals Integrated Analysis of MicroRNA (miRNA) and mRNA Profiles Reveals Reduced Correlation between MicroRNA and Target Gene in Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Xingsong Li ◽  
Xiaokang Yu ◽  
Yuting He ◽  
Yuhuan Meng ◽  
Jinsheng Liang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Mirna Target ◽  
Target Gene ◽  
Target Genes ◽  
Integrated Analysis ◽  
Cancer Type ◽  
Gene Pairs ◽  
Cancer Types

Background. Accumulating evidences demonstrated that microRNA-target gene pairs were closely related to tumorigenesis and development. However, the correlation between miRNA and target gene was insufficiently understood, especially its changes between tumor and normal tissues. Objectives. The aim of this study was to evaluate the changes of correlation of miRNAs-target pairs between normal and tumor. Materials and Methods. 5680 mRNA and 5740 miRNA expression profiles of 11 major human cancers were downloaded from the Cancer Genome Atlas (TCGA). The 11 cancer types were bladder urothelial carcinoma, breast invasive carcinoma, head and neck squamous cell carcinoma, kidney chromophobe, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, stomach adenocarcinoma, and thyroid carcinoma. For each cancer type, we firstly obtained differentially expressed miRNAs (DEMs) and genes (DEGs) in tumor and then acquired critical miRNA-target gene pairs by combining DEMs, DEGs and two experimentally validated miRNA-target interaction databases, miRTarBase and miRecords. We collected samples with both miRNA and mRNA expression values and performed a correlation analysis by Pearson method for miRNA-target pairs in normal and tumor, respectively. Results. We totally got 4743 critical miRNA-target pairs across 11 cancer types, and 4572 of them showed weaker correlation in tumor than in normal. The average correlation coefficients of miRNA-target pairs were different greatly between normal (-0.38 ~ -0.61) and tumor (-0.04 ~ -0.26) for 11 cancer type. The pan-cancer network, which consisted of 108 edges connecting 35 miRNAs and 89 target genes, showed the interactions of pairs appeared in multicancers. Conclusions. This comprehensive analysis revealed that correlation between miRNAs and target genes was greatly reduced in tumor and these critical pairs we got were involved in cellular adhesion, proliferation, and migration. Our research could provide opportunities for investigating cancer molecular regulatory mechanism and seeking therapeutic targets.

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