Hyperglycemia-induced changes in miRNA expression patterns in epicardial adipose tissue of piglets

MicroRNAs (miRNAs) are a class of molecular posttranscriptional regulators found to participate in numerous biological mechanisms, such as adipogenesis, fat deposition, or glucose metabolism. Additionally, a detailed analysis on the molecular and cellular mechanisms of miRNA-related effects on metabolism leads to developing novel diagnostic markers and therapeutic approaches. To identify miRNA whose activity changed in epicardial adipose tissue in piglets during hyperglycemia, we analyzed the different miRNA expression patterns between control and hyperglycemia groups. The microarray analysis selected three differentially expressed microRNAs as potential biomarkers: hsa-miR-675-5p, ssc-miR-193a-3p, and hsa-miR-144-3p. The validation of miRNA expression with real-time PCR indicated an increased expression levels of ssc-miR-193a-3p and miR-675-5p, whereas the expression level of hsa-miR-144-3p was lower in epicardial adipose tissue in response to hyperglycemia (P<0.01). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses suggested that these miRNAs differentially expressed between hyperglycemic and control piglets are involved in insulin, adipocytokine, and phosphatidylinositol 3-kinase–Akt signaling pathways, and development of type 2 diabetes as well. The results suggested that hyperglycemia can significantly affect the expression patterns of miRNA in porcine adipose tissue.

Download Full-text

Expression Profile of Circular RNAs in Epicardial Adipose Tissue in Heart Failure

10.1101/764266 ◽

2019 ◽

Author(s):

Meili Zheng ◽

Lei Zhao ◽

Xinchun Yang

Keyword(s):

Heart Failure ◽

Adipose Tissue ◽

Expression Profile ◽

Epicardial Adipose Tissue ◽

Expression Profiles ◽

Expression Patterns ◽

Circular Rna ◽

Circular Rnas ◽

Artery Disease ◽

Pathway Analyses

AbstractRecent studies have reported circular RNA (circRNA) expression profiles in various tissue types; specifically, a recent work showed a detailed circRNA expression landscape in the heart. However, circRNA expression profile in human epicardial adipose tissue (EAT) remains undefined. RNA-sequencing was carried out to compare circRNA expression patterns in EAT specimens from coronary artery disease (CAD) cases between the heart failure (HF) and non-HF groups. The top highly expressed EAT circRNAs corresponded to genes involved in cell proliferation and inflammatory response, including KIAA0182, RHOBTB3, HIPK3, UBXN7, PCMTD1, N4BP2L2, CFLAR, EPB41L2, FCHO2, FNDC3B and SPECC1. Among the 141 circRNAs substantially different between the HF and non-HF groups (P<0.05;fold change>2), hsa_circ_0005565 stood out, and was mostly associated with positive regulation of metabolic processes and insulin resistancein GO and KEGG pathway analyses, respectively. These data indicate EAT circRNAs contribute to the pathogenesis of metabolic disorders causing HF.

Download Full-text

Microarray Profiling of TGF-β1-Induced Long Non-Coding RNA Expression Patterns in Human Lung Bronchial Epithelial BEAS-2B Cells

Cellular Physiology and Biochemistry ◽

10.1159/000495052 ◽

2018 ◽

Vol 50 (6) ◽

pp. 2071-2085 ◽

Cited By ~ 4

Author(s):

Wentao Hu ◽

Weiwei Pei ◽

Lin Zhu ◽

Jing Nie ◽

Hailong Pei ◽

...

Keyword(s):

Human Lung ◽

Expression Patterns ◽

Differentially Expressed ◽

Bronchial Epithelial ◽

Qrt Pcr ◽

Microarray Profiling ◽

Underlying Mechanisms ◽

Pathway Analyses ◽

Trans Regulation ◽

Tgf Β1

Background/Aims: TGF-β1 mediated radiation-induced bystander effects (RIBE) have been linked with malignant transformation and tumorigenesis. However, the underlying mechanisms are not fully understood. Methods: To reveal new molecules of regulatory functions in this process, lncRNA microarray was performed to profile both lncRNA and mRNA expression patterns in human lung bronchial epithelial BEAS-2B cells treated with TGF-β1 at a concentration measured in the medium conditioned by directly irradiated BEAS-2B cells. The potential functions of the differentially expressed lncRNAs were predicted by GO and KEGG pathway analyses of their co-expressed mRNAs. Cis- and trans-regulation of the lncRNAs were analyzed and the interaction networks were constructed using Cytoscape. qRT-PCR was conducted to validate the results of microarray profiling. CCK-8 assay was employed for functional validation of 3 identified lncRNAs. Results: 224 lncRNAs were found to be dysregulated, among which 6 lncRNAs were chosen for expression validation by qRT-PCR assay. Pathway analyses showed that differentially expressed lncRNAs are highly correlated with cell proliferation, transformation, migration, etc. Trans-regulation analyses showed that the differentially expressed lncRNAs most likely participate in the pathways regulated by four transcriptional factors, FOS, STAT3, RAD21 and E2F1, which have been identified to be involved in the modulation of oncogenic transformation, cell cycle progression, genomic instability, etc. lnc-THEMIS-2 and lnc-ITGB6-4, predicted to be regulated by STAT3 and E2F1 respectively, were found to rescue the decrease of cell viability induced by TGF-β1 treatment. Conclusion: Our findings suggest that the differentially expressed lncRNAs induced by TGF-β1 play crucial roles in the oncogenic transformation and tumorigenesis, which provide a better understanding of the underlying mechanisms related to tumorigensis induced by LD/LDR radiations.

Download Full-text

Small RNA Sequencing Reveals Differentially Expressed miRNAs in Necrotizing Enterocolitis in Rats

BioMed Research International ◽

10.1155/2020/5150869 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Ren-qiang Yu ◽

Min Wang ◽

Shan-yu Jiang ◽

Ying-hui Zhang ◽

Xiao-yu Zhou ◽

...

Keyword(s):

Wnt Signaling ◽

Signaling Pathway ◽

Rna Sequencing ◽

Necrotizing Enterocolitis ◽

Small Rna ◽

Mirna Expression ◽

Expression Patterns ◽

Wnt Signaling Pathway ◽

Differentially Expressed ◽

Small Rna Sequencing

Necrotizing enterocolitis (NEC) is the leading cause of death due to gastrointestinal disease in preterm infants. The role of miRNAs in NEC is still unknown. The objective of this study was to identify differentially expressed (DE) miRNAs in rats with NEC and analyze their possible roles. In this study, a NEC rat model was established using Sprague-Dawley rat pups. Small RNA sequencing was used to analyze the miRNA expression profiles in the NEC and control rats. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out to identify target mRNAs for the DE miRNAs and to explore their potential roles. The DE miRNAs were verified by real-time quantitative PCR (RT-qPCR). The status of intestinal injury and the elevated levels of inflammatory cytokines in the NEC group confirmed that the NEC model was successfully established. The 16 miRNAs were found to be differentially expressed between the NEC group and the control group of rats. Bioinformatics analysis indicated that the parental genes of the DE miRNAs were predominantly implicated in the phosphorylation, cell migration, and protein phosphorylation processes. Moreover, the DE miRNAs were mainly found to be involved in the pathways of axon guidance, endocytosis, and focal adhesion, as well as in the Wnt signaling pathway, which is related to colitis. The expression patterns of the candidate miRNAs (rno-miR-27a-5p and rno-miR-187-3p), as assessed by RT-qPCR, were in accordance with the expression patterns obtained by miRNA-sequencing. The miRNA/mRNA/pathway network revealed that rno-miR-27a-5p and rno-miR-187-3p might be involved in NEC via the Wnt signaling pathway. We found an altered miRNA expression pattern in rats with NEC. We hypothesize that rno-miR-27a-5p and rno-miR-187-3p might mediate the NEC pathophysiological processes via the Wnt signaling pathway.

Download Full-text

Analysis of microRNA Patterns in Hodgkin’s Lymphoma (HL).

Blood ◽

10.1182/blood.v108.11.474.474 ◽

2006 ◽

Vol 108 (11) ◽

pp. 474-474

Author(s):

Alfons Navarro ◽

Anna Gaya ◽

Aina Pons ◽

Pau Abrisqueta ◽

Bernat Gel ◽

...

Keyword(s):

Lymph Nodes ◽

Mirna Expression ◽

Cellular Proliferation ◽

Clinical Stage ◽

Expression Patterns ◽

Differentially Expressed ◽

Apoptotic Pathway ◽

Apoptosis Pathway ◽

Differentially Expressed Mirnas ◽

Clinical Stages

Abstract Mature microRNAs (miRNA) are recently discovered small RNA molecules of 21–25 nucleotides in length. They act as negative regulators of expression of important genes like those participating in cellular proliferation or apoptosis. There is evidence that miRNA play an important role in carcinogenesis. The objective of this study was to compare the miRNA expression patterns in normal lymph nodes and in lymph nodes from patients with HL. Moreover, we investigated the miRNA pattern of HL depending on Epstein-Barr Virus (EBV) expression. We assessed 156 mature miRNAs by Stem-loop RT-PCR and Real time PCR in ABI PRISM 7500 in 9 normal lymph nodes and 39 patients diagnosed with HL nodular sclerosis subtype (15 EBV+ and 24 EBV-)at a single institution. Patients median age was 27 years (range, 15–52), and clinical stage was I (n=1); II (n=22); III (n=8) and IV (n=8); 41% of the patients reported B symptoms. RNA was obtained in all cases from formalin fixed paraffin embedded tissues. miRNA expression data was normalized to let-7a miRNA and to global median. Relative quantification of miRNA expression was calculated with the 2−ΔΔCt method. The data were presented as log10 of relative quantity of target miRNA. Normal human lymph node tissue was used as calibrator for all samples. Data were analyzed by means of Significant Analysis of Microarrays (SAM), Student’s t-test (with random variance model) and Class prediction methods using BRB Array Tools version 3.4.0 and TIGR Multiexperiment Viewer version 3.1. Of the 156 miRNAs analyzed, 35 were differentially expressed between normal lymph nodes and HL (12 miRNAs were upregulated and 23 downregulated). The most differentially overexpressed miRNAs was miR-216, which inhibits apoptosis pathway. Other differentially expressed miRNAs were miR-140, 204, 19a, 20, 191 and 142-3p, which have been associated to the genesis of hematological and non-hematological malignances. With respect to EBV+ vs. EBV− cases, we found that miR-96 and miR-335 were underexpressed in the EBV+ cases as compared to EBV− (p=0.001). These miRNAs have RNF34 and BIRC2 genes as targets, which have an antiapoptotic function. We also found that miR-138 was more frequently overexpressed in clinical stages I–II versus clinical stages III–IV (p=0.004), and that miR-328 was more frequently overexpressed in stages III–IV (p=0.004). In conclusion, miRNAs might have a role in the pathogenesis of HL. The miRNA pattern is different between the EBV+ and EBV− cases, and the differentially expressed miRNAs seems to be related to the apoptotic pathway.

Download Full-text

MicroRNA expression patterns associated with hyperfunctioning and non-hyperfunctioning phenotypes in adrenocortical adenomas

Acta Endocrinologica ◽

10.1530/eje-13-0817 ◽

2014 ◽

Vol 170 (4) ◽

pp. 583-591 ◽

Cited By ~ 12

Author(s):

David Velázquez-Fernández ◽

Stefano Caramuta ◽

Deniz M Özata ◽

Ming Lu ◽

Anders Höög ◽

...

Keyword(s):

Mirna Expression ◽

Expression Profiles ◽

Expression Patterns ◽

Gene Mutations ◽

Mirna Expression Profile ◽

Differentially Expressed ◽

Adrenocortical Adenoma ◽

Tumor Subtypes ◽

Mirna Expression Profiles ◽

Differentially Expressed Mirnas

BackgroundThe adrenocortical adenoma (ACA) entity includes aldosterone-producing adenoma (APA), cortisol-producing adenoma (CPA), and non-hyperfunctioning adenoma (NHFA) phenotypes. While gene mutations and mRNA expression profiles have been partly characterized, less is known about the alterations involving microRNA (miRNA) expression.AimTo characterize miRNA expression profile in relation to the subtypes of ACAs.Subjects and methodsmiRNA expression profiles were determined in 26 ACAs (nine APAs, ten CPAs, and seven NHFAs) and four adrenal references using microarray-based screening. Significance analysis of microarrays (SAM) was carried out to identify differentially expressed miRNAs between ACA and adrenal cortices or between tumor subtypes. Selected differentially expressed miRNAs were validated in an extended series of 43 ACAs and ten adrenal references by quantitative RT-PCR.ResultsAn hierarchical clustering revealed separate clusters for APAs and CPAs, while the NHFAs were found spread out within the APA/CPA clusters. When NHFA was excluded, the clustering analysis showed a better separation between APA and CPA. SAM analysis identified 40 over-expressed and three under-expressed miRNAs in the adenomas as compared with adrenal references. Fourteen miRNAs were common among the three ACA subtypes. Furthermore, we found specific miRNAs associated with different tumor phenotypes.ConclusionThe results suggest that miRNA expression profiles can distinguish different subtypes of ACA, which may contribute to a deeper understanding of ACA development and potential therapeutics.

Download Full-text

Next-generation sequencing analysis reveals segmental patterns of microRNA expression in yak epididymis

Reproduction Fertility and Development ◽

10.1071/rd20113 ◽

2020 ◽

Vol 32 (12) ◽

pp. 1067

Author(s):

Wangsheng Zhao ◽

Eugene Quansah ◽

Meng Yuan ◽

Pengcheng Li ◽

Chuanping Yi ◽

...

Keyword(s):

Gene Expression ◽

Mirna Expression ◽

Expression Patterns ◽

Differentially Expressed ◽

Sequencing Analysis ◽

Differentially Expressed Mirnas ◽

Next Generation Sequencing Analysis ◽

Cauda Epididymidis ◽

Caput Epididymidis

MicroRNAs (miRNAs) have emerged as potent regulators of gene expression and are widely expressed in biological systems. In reproduction, they have been shown to have a significant role in the acquisition and maintenance of male fertility, whereby deletion of Dicer in mouse germ cells leads to infertility. Evidence indicates that this role of miRNAs extends from the testis into the epididymis, controlling gene expression and contributing to regional variations in gene expression. In this study, RNA sequencing technology was used to investigate miRNA expression patterns in the yak epididymis. Region-specific miRNA expression was found in the yak epididymis. In all, 683 differentially expressed known miRNAs were obtained; 190, 186 and 307 differentially expressed miRNAs were identified for caput versus corpus, corpus versus cauda and caput versus cauda region pairs respectively. Kyoto Encyclopedia of Genes and Genomes results showed endocytosis as the most enriched pathway across region pairs, followed by protein processing in the endoplasmic reticulum, phagosome, spliceosome and biosynthesis of amino acids in region pair-specific hierarchical order. Gene ontology results showed varied enrichment in terms including cell, biogenesis, localisation, binding and locomotion across region pairs. In addition, significantly higher miR-34c expression was seen in the yak caput epididymidis relative to the corpus and cauda epididymidis.

Download Full-text

Differences in microRNA Changes of Healthy Rat Liver between Sevoflurane and Propofol Anesthesia

Anesthesiology ◽

10.1097/aln.0b013e3182746676 ◽

2012 ◽

Vol 117 (6) ◽

pp. 1245-1252 ◽

Cited By ~ 31

Author(s):

Masashi Ishikawa ◽

Shunsuke Tanaka ◽

Masae Arai ◽

Yuuki Genda ◽

Atsuhiro Sakamoto

Keyword(s):

Rat Liver ◽

Mirna Expression ◽

Control Cell ◽

Mirna Expression Profile ◽

Differentially Expressed ◽

Screening Tests ◽

Control Group ◽

Low Density ◽

Mirna Expression Pattern ◽

And Control

Background In previous studies, the authors showed that anesthetics affect the expression ratios of many genes in rat liver. microRNAs (miRNA) negatively regulate more than 30% of genes in cells, and control cell proliferation, inflammation, and metabolism. The authors hypothesized that anesthetics influence miRNA expression in the liver, and performed miRNA screening tests using TaqMan low-density arrays. Methods Rats were randomly assigned to the 2.4% sevoflurane group, the 600 µg·kg⁻¹·min⁻¹ propofol group, and the control group without anesthetics. Rats were allowed to breathe spontaneously under anesthesia for 6 h. The miRNA expression profile of the liver was analyzed, and 15 representative miRNAs were validated by quantitative real-time reverse transcriptase polymerase chain reaction. Results TaqMan low-density arrays analysis showed 46 miRNAs that were differentially expressed by anesthetics. After sevoflurane treatment, 16 miRNAs were significantly increased and 11 were significantly decreased compared with controls, whereas after propofol treatment, 31 miRNAs were increased and 8 were decreased. Twenty expressed miRNAs were common to both anesthetics, whereas three miRNAs were differentially expressed. Bland-Altman analysis was performed across the validations to compare the fold changes measured by both methods, and they were equivalent (mean difference=0.01, 95% CI=-0.26 to 0.27). This showed that the TaqMan low-density arrays results are accurate and can be confirmed using an independent experimental approach. Conclusion The results showed that anesthetics cause many miRNA expression changes, and the miRNA expression pattern was particular for each anesthetic. Further studies are needed to determine the functional consequence of miRNA modulation by anesthetics.

Download Full-text

Characteristics of microRNAs enriched in specific cell types and primary tissue types in solid organs

Physiological Genomics ◽

10.1152/physiolgenomics.00090.2013 ◽

2013 ◽

Vol 45 (23) ◽

pp. 1144-1156 ◽

Cited By ~ 17

Author(s):

Alison J. Kriegel ◽

Yong Liu ◽

Pengyuan Liu ◽

Maria Angeles Baker ◽

Matthew R. Hodges ◽

...

Keyword(s):

Mirna Expression ◽

Expression Patterns ◽

Cell Types ◽

Differentially Expressed ◽

Tissue Type ◽

Motor Nucleus ◽

Specific Cell ◽

Thick Ascending Limb ◽

Cell Type ◽

Primary Tissue

Knowledge of miRNA expression and function in specific cell types in solid organs is limited because of difficulty in obtaining appropriate specimens. We used laser capture microdissection to obtain nine tissue regions from rats, including the nucleus of the solitary tract, hypoglossal motor nucleus, ventral respiratory column/pre-Bötzinger complex, and midline raphe nucleus from the brain stem, myocardium and coronary artery from the heart, and glomerulus, proximal convoluted tubule, and medullary thick ascending limb from the kidney. Each tissue region consists of or is enriched for a specific cell type. Differential patterns of miRNA expression obtained by deep sequencing of minute amounts of laser-captured cells were highly consistent with data obtained from real-time PCR analysis. miRNA expression patterns correctly clustered the specimens by tissue regions and then by primary tissue types (neural, muscular, or epithelial). The aggregate difference in miRNA profiles between tissue regions that contained the same primary tissue type was as large as one-half of the aggregate difference between primary tissue types. miRNAs differentially expressed between primary tissue types are more likely to be abundant miRNAs, while miRNAs differentially expressed between tissue regions containing the same primary tissue type were distributed evenly across the abundance spectrum. The tissue type-enriched miRNAs were more likely to target genes enriched for specific functional categories compared with either cell type-enriched miRNAs or randomly selected miRNAs. These data indicate that the role of miRNAs in determining characteristics of primary tissue types may be different than their role in regulating cell type-specific functions in solid organs.

Download Full-text

Changes in Gene Expression during G-CSF-Induced Emergency Granulopoiesis in Humans

Blood ◽

10.1182/blood.v126.23.2202.2202 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2202-2202

Author(s):

Corinna Cavan Pedersen ◽

Rehannah Borup ◽

Anne Fischer-Nielsen ◽

Helena Mora-Jensen ◽

Anna Fossum ◽

...

Keyword(s):

Bone Marrow ◽

Mirna Expression ◽

Conflicts Of Interest ◽

Expression Patterns ◽

Critical Role ◽

Severe Infection ◽

Mrna Levels ◽

Healthy Individuals ◽

Induced Changes

Abstract Emergency granulopoiesis refers to the increased production of neutrophils in bone marrow and their release into circulation induced by severe infection. Several studies point to a critical role for granulocyte colony-stimulating factor (G-CSF) as the main mediator of emergency granulopoiesis. However, the consequences of G-CSF stimulation on the transcriptome of neutrophils and their precursors have not yet been elucidated in humans. Here, we investigate the changes in mRNA and miRNA expression in successive stages of neutrophil development following in vivo administration of G-CSF in humans, mimicking emergency granulopoiesis. Blood samples were collected from healthy individuals after five days of G-CSF administration. Neutrophil precursors were sorted into discrete stages of maturation by flow cytometry and extracted RNA was subjected to microarray analysis. mRNA levels were compared to previously published expression levels in corresponding populations of neutrophil precursors isolated from bone marrow of untreated, healthy individuals. miRNA expression was investigated in the most mature cell population to determine G-CSF-induced changes in circulating neutrophils. G-CSF substantially affected mRNA and miRNA expression patterns, demonstrating significant impact on neutrophil development and function. 1110 mRNAs were differentially expressed more than 2-fold with G-CSF while the treatment induced changes in the levels of 73 miRNAs in the mature population. In addition, G-CSF treatment reduced the levels of four out of five measured granule proteins in mature neutrophils including hCAP-18, which was completely deficient in neutrophils from G-CSF-treated donors. Cell cycle analysis pointed towards an induced proliferative capacity of myelocytes. These results indicate that multiple biological processes are altered in order to satisfy the increased demand for neutrophils during G-CSF-induced emergency granulopoiesis. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Genome-wide profiling of miRNA expression patterns in tubal endometriosis

Reproduction ◽

10.1530/rep-18-0631 ◽

2019 ◽

Vol 157 (6) ◽

pp. 525-534 ◽

Cited By ~ 4

Author(s):

Hang Qi ◽

Guiling Liang ◽

Jin Yu ◽

Xiaofeng Wang ◽

Yan Liang ◽

...

Keyword(s):

Pathway Analysis ◽

Mirna Expression ◽

Gene Networks ◽

Target Genes ◽

Expression Profiles ◽

Expression Patterns ◽

Mirna Gene ◽

Differentially Expressed ◽

Signal Pathways ◽

Differentially Expressed Mirnas

MicroRNA (miRNA) expression proﬁles in tubal endometriosis (EM) are still poorly understood. In this study, we analyzed the differential expression of miRNAs and the related gene networks and signaling pathways in tubal EM. Four tubal epithelium samples from tubal EM patients and five normal tubal epithelium samples from uterine leiomyoma patients were collected for miRNA microarray. Bioinformatics analyses, including Ingenuity Pathway Analysis (IPA), Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) validation of five miRNAs was performed in six tubal epithelium samples from tubal EM and six from control. A total of 17 significantly differentially expressed miRNAs and 4343 potential miRNA-target genes involved in tubal EM were identified (fold change >1.5 and FDR-adjustedPvalue <0.05). IPA indicated connections between miRNAs, target genes and other gynecological diseases like endometrial carcinoma. GO and KEGG analysis revealed that most of the identified genes were involved in the mTOR signaling pathway, SNARE interactions in vesicular transport and endocytosis. We constructed an miRNA-gene-disease network using target gene prediction. Functional analysis showed that the mTOR pathway was connected closely to tubal EM. Our results demonstrate for the first time the differentially expressed miRNAs and the related signal pathways involved in the pathogenesis of tubal EM which contribute to elucidating the pathogenic mechanism of tubal EM-related infertility.

Download Full-text