The Regulatory Mechanism of Feeding a Diet High in Rice Grain on the Growth and microRNA Expression Profiles of the Spleen, Taking Goats as an Artiodactyl Model

Several researchers have testified that feeding with diets high in rice grain induces subacute ruminal acidosis and increases the risk of gastrointestinal inflammation. However, whether diets high in rice grain affect spleen growth and related molecular events remains unknown. Therefore, the present study was conducted to investigate the effects of feeding a high-concentrate (HC) diet based on rice on the growth and microRNA expression profiles in goat spleen. Sixteen Liuyang black goats were used as an artiodactyl model and fed an HC diet for five weeks. Visceral organ weight, LPS (lipopolysaccharide) concentration in the liver and spleen, and microRNA expression were analyzed. The results showed that feeding an HC diet increased the heart and spleen indexes and decreased the liver LPS concentration (p < 0.05). In total, 596 microRNAs were identified, and twenty-one of them were differentially expressed in the spleens of goats fed with the HC diet. Specifically, several microRNAs (miR-107, miR-512, miR-51b, miR-191, miR-296, miR-326, miR-6123 and miR-433) were upregulated. Meanwhile, miR-30b, miR-30d, miR-1468, miR-502a, miR-145, miR-139, miR-2284f, miR-101 and miR-92a were downregulated. Additionally, their target gene CPPED1, CDK6, CCNT1 and CASP7 expressions were inhibited (p < 0.05). These results indicated that the HC diet promoted the growth of the heart and spleen. The HC diet also regulated the expression of miR-326, miR-512-3p, miR-30b, miR-30d, miR-502a and their target genes (CPPED1, CDK6 and CCNT1) related to the enhancement of splenocyte proliferation. The HC diet also modulated the expression of miR-15b-5p, miR-1468 and miR-92a, related to the suppression of splenocyte apoptosis.

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Identification of Tumorigenic and Prognostic Biomarkers in Colorectal Cancer Based on microRNA Expression Profiles

BioMed Research International ◽

10.1155/2020/7136049 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Yuntao Shi ◽

Yingying Zhuang ◽

Jialing Zhang ◽

Mengxue Chen ◽

Shangnong Wu

Keyword(s):

Target Genes ◽

Cox Regression ◽

Expression Profiles ◽

Survival Rates ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Risk Groups ◽

Normal Mucosa ◽

Microrna Expression ◽

Functional Enrichment

Objective. Although noncoding RNAs, especially the microRNAs, have been found to play key roles in CRC development in intestinal tissue, the specific mechanism of these microRNAs has not been fully understood. Methods. GEO and TCGA database were used to explore the microRNA expression profiles of normal mucosa, adenoma, and carcinoma. And the differential expression genes were selected. Computationally, we built the SVM model and multivariable Cox regression model to evaluate the performance of tumorigenic microRNAs in discriminating the adenomas from normal tissues and risk prediction. Results. In this study, we identified 20 miRNA biomarkers dysregulated in the colon adenomas. The functional enrichment analysis showed that MAPK activity and MAPK cascade were highly enriched by these tumorigenic microRNAs. We also investigated the target genes of the tumorigenic microRNAs. Eleven genes, including PIGF, TPI1, KLF4, RARS, PCBP2, EIF5A, HK2, RAVER2, HMGN1, MAPK6, and NDUFA2, were identified to be frequently targeted by the tumorigenic microRNAs. The high AUC value and distinct overall survival rates between the two risk groups suggested that these tumorigenic microRNAs had the potential of diagnostic and prognostic value in CRC. Conclusions. The present study revealed possible mechanisms and pathways that may contribute to tumorigenesis of CRC, which could not only be used as CRC early detection biomarkers, but also be useful for tumorigenesis mechanism studies.

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Effect of miR-27b-5p on apoptosis of human vascular endothelial cells induced by simulated microgravity

APOPTOSIS ◽

10.1007/s10495-019-01580-6 ◽

2019 ◽

Vol 25 (1-2) ◽

pp. 73-91 ◽

Cited By ~ 1

Author(s):

Yi-Kai Pan ◽

Cheng-Fei Li ◽

Yuan Gao ◽

Yong-Chun Wang ◽

Xi-Qing Sun

Keyword(s):

Endothelial Cells ◽

Western Blot ◽

Target Gene ◽

Simulated Microgravity ◽

Target Genes ◽

Expression Profiles ◽

Differentially Expressed ◽

Luciferase Assay ◽

Qrt Pcr ◽

Differentially Expressed Mirnas

AbstractWeightlessness-induced cardiovascular dysfunction can lead to physiological and pathological consequences. It has been shown that spaceflight or simulated microgravity can alter expression profiles of some microRNAs (miRNAs). Here, we attempt to identify the role of miRNAs in human umbilical vein endothelial cells (HUVECs) apoptosis under simulated microgravity. RNA-sequencing and quantitative real-time PCR (qRT-PCR) assays were used to identify differentially expressed miRNAs in HUVECs under simulated microgravity. Then we obtained the target genes of these miRNAs through target analysis software. Moreover, GO and KEGG enrichment analysis were performed. The effects of these miRNAs on HUVECs apoptosis were evaluated by flow cytometry, Western blot and Hoechst staining. Furthermore, we obtained the target gene of miR-27b-5p by luciferase assay, qRT-PCR and Western blot. Finally, we investigated the relationship between this target gene and miR-27b-5p in HUVECs apoptosis under normal gravity or simulated microgravity. We found 29 differentially expressed miRNAs in HUVECs under simulated microgravity. Of them, the expressions of 3 miRNAs were validated by qRT-PCR. We demonstrated that miR-27b-5p affected HUVECs apoptosis by inhibiting zinc fingers and homeoboxes 1 (ZHX1). Our results reported here demonstrate for the first time that simulated microgravity can alter the expression of some miRNAs in HUVECs and miR-27b-5p may protect HUVECs from apoptosis under simulated microgravity by targeting ZHX1.

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A Network-Based Approach for Identification of Subtype-Specific Master Regulators in Pancreatic Ductal Adenocarcinoma

Genes ◽

10.3390/genes11020155 ◽

2020 ◽

Vol 11 (2) ◽

pp. 155

Author(s):

Yuchen Zhang ◽

Lina Zhu ◽

Xin Wang

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Network Inference ◽

Molecular Mechanisms ◽

Target Genes ◽

Regulatory Mechanism ◽

Expression Profiles ◽

Strong Association ◽

Predictive Biomarkers ◽

Integrative Analysis ◽

Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC), the predominant subtype of pancreatic cancer, has been reported with equal mortality and incidence for decades. The lethality of PDAC is largely due to its late presentation, when surgical resection is no longer an option. Similar to other major malignancies, it is now clear that PDAC is not a single disease, posing a great challenge to precise selection of patients for optimized adjuvant therapy. A representative study found that PDAC comprises four distinct molecular subtypes: squamous, pancreatic progenitor, immunogenic, and aberrantly differentiated endocrine exocrine (ADEX). However, little is known about the molecular mechanisms underlying specific PDAC subtypes, hampering the design of novel targeted agents. In this study we performed network inference that integrates miRNA expression and gene expression profiles to dissect the miRNA regulatory mechanism specific to the most aggressive squamous subtype of PDAC. Master regulatory analysis revealed that the particular subtype of PDAC is predominantly influenced by miR-29c and miR-192. Further integrative analysis found miR-29c target genes LOXL2, ADAM12 and SERPINH1, which all showed strong association with prognosis. Furthermore, we have preliminarily revealed that the PDAC cell lines with high expression of these miRNA target genes showed significantly lower sensitivities to multiple anti-tumor drugs. Together, our integrative analysis elucidated the squamous subtype-specific regulatory mechanism, and identified master regulatory miRNAs and their downstream genes, which are potential prognostic and predictive biomarkers.

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Analysis of Long Noncoding RNA and mRNA Expression Profiles of Testes with High and Low Sperm Motility in Domestic Pigeons (Columba livia)

Genes ◽

10.3390/genes11040349 ◽

2020 ◽

Vol 11 (4) ◽

pp. 349

Author(s):

Xiuli Xu ◽

Yuge Tan ◽

Haiguang Mao ◽

Honghua Liu ◽

Xinyang Dong ◽

...

Keyword(s):

Sperm Motility ◽

Noncoding Rna ◽

Target Gene ◽

Target Genes ◽

Semen Quality ◽

Expression Profiles ◽

Columba Livia ◽

Ion Binding ◽

Biological Processes ◽

Domestic Pigeons

Sperm motility is one of the most important indicators in assessing semen quality, and it is used to evaluate poultry fertility. Many long noncoding RNAs (lncRNAs) and mRNAs are involved in regulating testis development and spermatogenesis. In this study, we employed RNA sequencing to analyse the testis transcriptome (lncRNA and mRNA) of ten pigeons with high and low sperm motility. In total, 46,117 mRNAs and 17,463 lncRNAs were identified, of which 2673 mRNAs and 229 lncRNAs (P < 0.05) were significantly differentially expressed (DE) between the high and low sperm motility groups. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analysis showed that target genes of DE lncRNAs and DE mRNAs were related to calcium ion binding, ATP binding, and spermatogenesis. Moreover, we found that UBB, a target gene of lncRNA MSTRG.7787.5, was involved in germ cell development. Our study provided a catalogue of lncRNAs and mRNAs associated with sperm motility, and they deserve further study to deepen the understanding of biological processes in the pigeon testis.

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Identification and Evaluation of Reference Genes for Normalization of Gene Expression in Developmental Stages, Sexes, and Tissues of Diaphania caesalis (Lepidoptera, Pyralidae)

Journal of Insect Science ◽

10.1093/jisesa/iez130 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Zheng Wang ◽

Qianqian Meng ◽

Xi Zhu ◽

Shiwei Sun ◽

Aiqin Liu ◽

...

Keyword(s):

Gene Expression ◽

Reference Genes ◽

Target Gene ◽

Target Genes ◽

Developmental Stages ◽

Expression Profiles ◽

Transcriptional Level ◽

Internal Reference ◽

Target Gene Expression ◽

Qrt Pcr

Abstract Diaphania caesalis (Walker) is an important boring insect mainly distributed in subtropical and tropical areas and attacked tropical woody grain crops, such as starchy plants of Artocarpus. Quantitative real-time polymerase chain reaction (qRT-PCR) is a powerful approach for investigating target genes expression profiles at the transcriptional level. However, the identification and selection of internal reference genes, which is often overlooked, is the most vital step before the analysis of target gene expression by qRT-PCR. So far, the reliable internal reference genes under a certain condition of D. caesalis have not been investigated. Therefore, this study evaluated the expression stability of eight candidate reference genes including ACT, β-TUB, GAPDH, G6PDH, RPS3a, RPL13a, EF1α, and EIF4A in different developmental stages, tissues and sexes using geNorm, NormFinder and BestKeeper algorithms. To verify the stability of the recommended internal reference genes, the expression levels of DcaeOBP5 were analyzed under different treatment conditions. The results indicated that ACT, RPL13a, β-TUB, RPS3a, and EF1α were identified as the most stable reference genes for further studies on target gene expression involving different developmental stages of D. caesalis. And ACT and EIF4A were recommended as stable reference genes for different tissues. Furthermore, ACT, EF1α, and RPS3a were ranked as the best reference genes in different sexes based on three algorithms. Our research represents the critical first step to normalize qRT-PCR data and ensure the accuracy of expression of target genes involved in phylogenetic and physiological mechanism at the transcriptional level in D. caesalia.

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ADAMTS-1: a novel target gene of an estrogen-induced transcription factor, EGR1, critical for embryo implantation in the mouse uterus

Cell & Bioscience ◽

10.1186/s13578-021-00672-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mira Park ◽

So Hee Park ◽

Hyunsun Park ◽

Hye-Ryun Kim ◽

Hyunjung J. Lim ◽

...

Keyword(s):

Transcription Factor ◽

Target Gene ◽

Target Genes ◽

Expression Profiles ◽

Embryo Implantation ◽

Uterine Epithelium ◽

Expression Vectors ◽

Dependent Manner ◽

Mouse Uterus ◽

Novel Target

Abstract Background Recently, we demonstrated that estrogen (E2) induces early growth response 1 (Egr1) to mediate its actions on the uterine epithelium by controlling progesterone receptor signaling for successful embryo implantation. EGR1 is a transcription factor that regulates the spectrum of target genes in many different tissues, including the uterus. E2-induced EGR1 regulates a set of genes involved in epithelial cell remodeling during embryo implantation in the uterus. However, only few target genes of EGR1 in the uterus have been identified. Result The expression of ADAM metallopeptidase with thrombospondin type 1 motif 1 (Adamts-1) was significantly downregulated in the uteri of E2-treated ovariectomized (OVX) Egr1(−/−) mice. Immunostaining of ADAMTS-1 revealed its exclusive expression in the uterine epithelium of OVX wild-type but not Egr1(−/−) mice treated with E2. The expression profiles of Adamts-1 and Egr1 were similar in the uteri of E2-treated OVX mice at various time points tested. Pre-treatment with ICI 182, 780, a nuclear estrogen receptor (ER) antagonist, effectively inhibited the E2-dependent induction of Egr1 and Adamts-1. Pharmacologic inhibition of E2-induced ERK1/2 or p38 phosphorylation interfered with the induction of EGR1 and ADAMTS-1. Furthermore, ADAMTS-1, as well as EGR1, was induced in stroma cells surrounding the implanting blastocyst during embryo implantation. Transient transfection with EGR1 expression vectors significantly induced the expression of ADAMTS-1. Luciferase activity of the Adamts-1 promoter containing EGR1 binding sites (EBSs) was increased by EGR1 in a dose-dependent manner, suggesting functional regulation of Adamts-1 transcription by EGR1. Site-directed mutagenesis of EBS on the Adamts-1 promoter demonstrated that EGR1 directly binds to the EBS at -1151/-1134 among four putative EBSs. Conclusions Collectively, we have demonstrated that Adamts-1 is a novel target gene of E2-ER-MAPK-EGR1, which is critical for embryo implantation in the mouse uterus during early pregnancy.

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Comparative Analysis of MicroRNA Expression Profiles Between Skeletal Muscle- and Adipose-Derived Exosomes in Pig

Frontiers in Genetics ◽

10.3389/fgene.2021.631230 ◽

2021 ◽

Vol 12 ◽

Author(s):

Weite Li ◽

Shulei Wen ◽

Jiahan Wu ◽

Bin Zeng ◽

Ting Chen ◽

...

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

High Throughput Sequencing ◽

Target Genes ◽

Expression Profiles ◽

Microrna Expression ◽

Skeletal Muscle Atrophy ◽

Adipose Tissues ◽

Regulation Of Metabolism ◽

Main Components

Skeletal muscle and adipose tissues are both involved in regulation of metabolism. In the skeletal muscle-adipose tissue crosstalk, exosomes may play an important role but the main components of exosomes are not clear. In this study, we found skeletal muscle-derived exosomes can inhibit adipogenesis of porcine preadipocytes. We identified microRNA expression profiles of muscle exosomes and adipose exosomes by high-throughput sequencing. There were 104 (both novel and known microRNAs) microRNAs differentially expressed (DE miRNAs) between M-EXO (muscle-derived exosomes) and A-EXO (adipose–derived exosomes) groups. A total of 2,137 target genes of DE miRNAs for M-EXO and 2,004 target genes of DE miRNAs for A-EXO were detected. Bioinformatic analyses revealed that some DE miRNAs of M-EXO (especially miR-221-5p) were mainly enriched in lipid-related metabolism processes. The findings may serve as a fundamental resource for understanding the detailed functions of exosomes between the skeletal muscle-adipose crosstalk and the potential relationship between skeletal muscle atrophy and obesity.

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MicroRNA Expression Profiles Identify Biomarker for Differentiating the Embolic Stroke from Thrombotic Stroke

BioMed Research International ◽

10.1155/2018/4514178 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 6

Author(s):

Lai-Te Chen ◽

Chen-Yang Jiang

Keyword(s):

Target Genes ◽

Expression Profiles ◽

Gene Expression Omnibus ◽

Microrna Expression ◽

Embolic Stroke ◽

Differentially Expressed ◽

Mitral Valve Stenosis ◽

Ppi Network ◽

Stroke Group ◽

Disease Related Genes

In order to identify potential biomarkers that distinguish the embolic stroke (ES) from thrombotic stroke (TS), a profile of microRNA expression was analyzed. The GSE60319 expression profile was downloaded from the Gene Expression Omnibus (GEO) database. The GEO2R was applied to screen for differentially expressed microRNAs (DEmiRNAs) between the embolic stroke group and thrombotic stroke group. The miRWalk was utilized to predict the target genes of DEmiRNAs. Genes associated with embolic stroke were downloaded from the Comparative Toxicogenomics Database. Cross reference of target genes to disease related genes was conducted to construct the DEmiRNA-gene network. The protein-protein interaction (PPI) network of overlapping genes was evaluated by STRING, using the MCODE and CytoHubba plugin of Cytoscape to identify the modules and hub genes. The enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) in modules was performed. There were 30 microRNAs in total identified as DEmiRNAs between embolic stroke and thrombotic stroke groups, of which 8 were upregulated and 22 were downregulated. Among these differentially expressed miRNAs, miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were significantly associated with an ES to TS. Using the miRWalk 3.0 online tool, target genes regulated by DEmiRNAs were predicted. In addition, disease related genes were predicted and compared with target genes of DEmiRNAs. 166 overlapped genes regulated by miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were identified, suggesting their association with diseases that contributed to ES, mainly including atrial fibrillation, mitral valve stenosis, myocardial infarction, and aortic dissection. Therefore, miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were promising candidate biomarkers for differentiating an ES from TS. The PPI network demonstrated that miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were associated with an ES by mainly regulating “CCND1, E2F2, E2F3, ITCH, UBE4A, UBE3C, RBL2, FBXO31, EIF2C4, and EIF2C1”. Furthermore, miR-15a-5p and miR-17-5p may function through “cell cycle, prostate cancer, and small cell lung cancer” while miR-19b-3p and miR-20a-5p function through “insulin resistance, hepatitis B, and viral carcinogenesis” and “vasopressin-regulated water reabsorption”, respectively. However, these results were approached in the manner of bioinformatics analysis; therefore, further verification is required.

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Human Prostate Tissue MicroRNAs and Their Predicted Target Pathways Linked to Prostate Cancer Risk Factors

Cancers ◽

10.3390/cancers13143537 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3537

Author(s):

Max Enwald ◽

Terho Lehtimäki ◽

Pashupati P. Mishra ◽

Nina Mononen ◽

Teemu J. Murtola ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Target Genes ◽

Expression Profiles ◽

Specific Antigen ◽

Prostate Cancer Risk ◽

Hdl Cholesterol ◽

Microrna Expression ◽

Prostate Tissue ◽

Multiple Testing Correction

MicroRNAs are important in prostate cancer development, progression and metastasis. The aim of this study was to test microRNA expression profile in prostate tissue obtained from prostate cancer patients for associations with various prostate cancer related factors and to pinpoint the predicted target pathways for these microRNAs. Prostate tissue samples were obtained at prostatectomy from patients participating in a trial evaluating impact of pre-operative atorvastatin on serum prostate specific antigen (PSA) and Ki-67 expression in prostate tissue. Prostate tissue microRNA expression profiles were analyzed using OpenArray® MicroRNA Panel. Pathway enrichment analyses were conducted for predicted target genes of microRNAs that correlated significantly with studied factors. Eight microRNAs correlated significantly with studied factors of patients after Bonferroni multiple testing correction. MiR-485-3p correlated with serum HDL-cholesterol levels. In atorvastatin-treated subjects, miR-34c-5p correlated with a change in serum PSA and miR-138-3p with a change in total cholesterol. In the placebo arm, both miR-576-3p and miR-550-3p correlated with HDL-cholesterol and miR-627 with PSA. In pathway analysis, these eight microRNAs related significantly to several pathways relevant to prostate cancer. This study brings new evidence from the expression of prostate tissue microRNAs and related pathways that may link risk factors to prostate cancer and pinpoint new therapeutic possibilities.

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Clustered, information-dense transcription factor binding sites identify genes with similar tissue-wide expression profiles

10.1101/283267 ◽

2018 ◽

Cited By ~ 2

Author(s):

Ruipeng Lu ◽

Peter K. Rogan

Keyword(s):

Gene Expression ◽

Machine Learning ◽

Transcription Factor ◽

Binding Site ◽

Target Gene ◽

Target Genes ◽

Gene Prediction ◽

Expression Profiles ◽

Expression Patterns ◽

Factor Binding

ABSTRACTBackgroundThe distribution and composition ofcis-regulatory modules (e.g. transcription factor binding site (TFBS) clusters) in promoters substantially determine gene expression patterns and TF targets, whose expression levels are significantly regulated by TF binding. TF knockdown experiments have revealed correlations between TF binding profiles and gene expression levels. We present a general framework capable of predicting genes with similar tissue-wide expression patterns from activated or repressed TF targets using machine learning to combine TF binding and epigenetic features.MethodsGenes with correlated expression patterns across 53 tissues were identified according to their Bray-Curtis similarity. DNase I HyperSensitive region (DHS) -accessible promoter intervals of direct TF target genes were scanned with previously derived information theory-based position weight matrices (iPWMs) of 82 TFs. Features from information density-based TFBS clusters were used to predict target genes with machine learning classifiers. The accuracy, specificity and sensitivity of the classifiers were determined for different feature sets. Mutations in TFBSs were also introduced to examine their impact on cluster densities and the regulatory states of predicted target genes.ResultsWe initially chose the glucocorticoid receptor gene (NR3C1), whose regulation has been extensively studied, to test this approach.SLC25A32andTANKwere found to exhibit the most similar expression patterns to this gene across 53 tissues. Prediction of other genes with similar expression profiles was significantly improved by eliminating inaccessible promoter intervals based on DHSs. A Random Forest classifier exhibited the best performance in detecting such coordinately regulated genes (accuracy was 0.972 for training, 0.976 for testing). Target gene prediction was confirmed using CRISPR knockdown data of TFs, which was more accurate than siRNA inactivation. Mutation analyses of TFBSs also revealed that one or more information-dense TFBS clusters in promoters are required for accurate target gene prediction.ConclusionsMachine learning based on TFBS information density, organization, and chromatin accessibility accurately identifies gene targets with comparable tissue-wide expression patterns. Multiple, information-dense TFBS clusters in promoters appear to protect promoters from the effects of deleterious binding site mutations in a single TFBS that would effectively alter the expression state of these genes.

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