scholarly journals Effects of Cardiac Sympathetic Neurodegeneration and PPARγ Activation on Rhesus Macaque Whole Blood miRNA and mRNA Expression Profiles

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Jeanette M. Metzger ◽  
Mary S. Lopez ◽  
Jenna K. Schmidt ◽  
Megan E. Murphy ◽  
Raghu Vemuganti ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Rhesus Macaque ◽  
Whole Blood ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Sympathetic Innervation ◽  
Sympathetic Denervation ◽  
Primate Model ◽  
Expression Levels ◽  
Cardiac Sympathetic Denervation

Degeneration of sympathetic innervation of the heart occurs in numerous diseases, including diabetes, idiopathic REM sleep disorder, and Parkinson’s disease (PD). In PD, cardiac sympathetic denervation occurs in 80-90% of patients and can begin before the onset of motor symptoms. Today, there are no disease-modifying therapies for cardiac sympathetic neurodegeneration, and biomarkers are limited to radioimaging techniques. Analysis of expression levels of coding mRNA and noncoding RNAs, such as microRNAs (miRNAs), can uncover pathways involved in disease, leading to the discovery of biomarkers, pathological mechanisms, and potential drug targets. Whole blood in particular is a clinically relevant source of biomarkers, as blood sampling is inexpensive and simple to perform. Our research group has previously developed a nonhuman primate model of cardiac sympathetic denervation by intravenous administration of the catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA). In this rhesus macaque (Macaca mulatta) model, imaging with positron emission tomography showed that oral administration of the peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone (n=5; 5 mg/kg daily) significantly decreased cardiac inflammation and oxidative stress compared to placebo (n=5). Here, we report our analysis of miRNA and mRNA expression levels over time in the whole blood of these monkeys. Differential expression of three miRNAs was induced by 6-OHDA (mml-miR-16-2-3p, mml-miR-133d-3p, and mml-miR-1262-5p) and two miRNAs by pioglitazone (mml-miR-204-5p and mml-miR-146b-5p) at 12 weeks posttoxin, while expression of mRNAs involved in inflammatory cytokines and receptors was not significantly affected. Overall, this study contributes to the characterization of rhesus coding and noncoding RNA profiles in normal and disease-like conditions, which may facilitate the identification and clinical translation of biomarkers of cardiac neurodegeneration and neuroprotection.

NEAT1 Is a Novel Oncogenic LncRNA and Correlated with miR-143 in Pediatric Oligodendrogliomas

2021 ◽  
Vol 56 (2) ◽  
pp. 133-139
Author(s):  
Secil Ak Aksoy ◽  
Melis Mutlu ◽  
Rabia Nur Balcin ◽  
Mevlut Ozgur Taskapilioglu ◽  
Cagla Tekin ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Pediatric Brain Tumors ◽  
Normal Brain ◽  
Diffuse Glioma ◽  
Expression Levels ◽  
Treatment Models ◽  
New Treatment

Introduction: The noncoding RNAs (ncRNAs) play a role in biological processes of various cancers including gliomas. The majority of these transcripts are uniquely expressed in differentiated tissues or specific glioma types. Pediatric oligodendroglioma (POG) is a rare subtype of diffuse glioma and accounts for <1% of pediatric brain tumors. Because histologically POG resembles adult OG, the same treatment is applied as adults. However, the significance in predicting outcomes in POG patients is unclear. In this study, we aimed to investigate the prognostic significance of expression ­profiles of microRNA (miRNA) and long noncoding RNA ­(LncRNA) in POGs. Methods: We investigated the levels of 13 known miRNAs and 6 LncRNAs in tumor samples from 9 patients with primary POG by using RT-PCR and analyzed their association with outcomes. Results: The expression levels of miR-21, miR-106a, miR-10b, and LncRNA NEAT1 were higher, and the expression level of miR-143 was lower in POG tissues compared with normal brain tissues (p = 0.006, p = 0.032, p = 0.034, p = 0.002, and p = 0.001, respectively). High levels of NEAT1 and low expression of miR-143 were associated with decreased probability of short disease-free survival (p = 0.018 and p = 0.022, respectively). Discussion: NEAT1 and miR-143 levels could serve as reciprocal prognostic predictors of disease progression in patients with POG. New treatment models to regulate the expression levels of NEAT1 and miR-143 will bring a new approach to the therapy of POG.

Genetic control of global gene expression levels in the intestinal mucosa: a human twin study

2009 ◽  
Vol 38 (1) ◽  
pp. 73-79 ◽  
Author(s):  
Robert Häsler ◽  
Alexander Begun ◽  
Sandra Freitag-Wolf ◽  
Martin Kerick ◽  
Nancy Mah ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Genetic Control ◽  
Intestinal Mucosa ◽  
Expression Profiles ◽  
Global Gene Expression ◽  
Model Organisms ◽  
Expression Levels ◽  
Molecular Phylogenetic ◽  
Health And Disease

Phenotypic variation between individuals, such as different mRNA expression levels, is influenced by genetic and nongenetic factors. Although several studies have addressed the interplay between genotypes and expression profiles in various model organisms in the recent years, the detailed and relative contributions of genetic and nongenetic factors in regulating plasticity of gene expression in barrier organs (e.g., skin, gut), which are exposed to continuous environmental challenge, are still poorly understood. Here we systematically monitored the level of genetic control over genomewide mRNA expression profiles in the healthy intestinal mucosa of 10 monozygotic and 10 dizygotic human twin pairs with microarray analyses. Our results, which are supported by real-time PCR and analysis of molecular phylogenetic conservation, indicate that genes associated with energy metabolism and cell and tissue regeneration pathways are under strong genetic control. Conversely, genes associated with immune response seem to be mainly controlled by exogenous factors. Further insights into the relative extent of genetic and nongenetic determinants of transcriptomal profiles and their influence on physiological and pathophysiological mechanisms are crucial to understanding the key role played by gene-environment interactions in health and disease.

scholarly journals Effects of Interleukin-1β on Long Noncoding RNA and mRNA Expression Profiles of Human Synovial Fluid-derived Mesenchymal Stem Cells

2021 ◽  
Author(s):  
Yang-peng Sun ◽  
Yun-yang Lu ◽  
Jianyu Chen ◽  
Jia-hao Bao ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Synovial Fluid ◽  
Mrna Expression ◽  
Temporomandibular Joint ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Biological Behavior ◽  
Antisense Lncrnas

Abstract Synovial fluid-derived mesenchymal stem cells (SFMSCs) play important regulatory roles in the physiological balance of the temporomandibular joint. Interleukin (IL)-1β regulates the biological behavior of SFMSCs; however, the effects of IL-1β on long noncoding RNA (lncRNA) and mRNA expression in SFMSCs in the temporomandibular joint are unclear. Here, we evaluated the lncRNA and mRNA expression profiles of IL-1β-stimulated SFMSCs. Using microarrays, we identified 286 lncRNAs (222 upregulated, 64 downregulated) and 304 mRNAs (242 upregulated, 62 downregulated) that were differentially expressed after treatment with IL-1β (fold change ≥ 2, P < 0.05). Kyoto Encyclopedia of Genes and Genomes pathway analysis found that one of the most significantly enriched pathways was the NF-κB pathway. Five paired antisense lncRNAs and mRNAs, eight paired enhancer lncRNAs and mRNAs, and nine paired long intergenic noncoding RNAs and mRNAs were predicted to be co-expressed. A network constructed by the top 30 k-score genes was visualized and evaluated. We found a co-expression relationship between ENST00000427824 and ENST00000307407 and between LOC541472 and IL6, which are related to NF-κB pathway activation. Overall, our results provide important insights into changes in lncRNA and mRNA expression in IL-1β-stimulated SFMSCs, which can facilitate the identification of potential therapeutic targets.

Long noncoding RNA‐mRNA expression profiles and validation in pancreatic neuroendocrine neoplasms

2020 ◽  
Vol 92 (4) ◽  
pp. 312-322 ◽  
Author(s):  
Meng Ji ◽  
Liang Tang ◽  
Rumei Ding ◽  
Ligang Shi ◽  
Anan Liu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Neuroendocrine Neoplasms ◽  
Pancreatic Neuroendocrine Neoplasms

Combination of Salinomycin and AZD3463 Reveals Synergistic Effect on Reducing the Viability of T98G Glioblastoma Cells

2020 ◽  
Vol 20 (18) ◽  
pp. 2267-2273 ◽  
Author(s):  
Aycan Asik ◽  
Neslihan P.O. Ay ◽  
Bakiye G. Bagca ◽  
Hasan O. Caglar ◽  
Cumhur Gunduz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Synergistic Effect ◽  
Wnt Signaling ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Combination Treatment ◽  
Expression Profiles ◽  
Wnt Signaling Pathway ◽  
Expression Levels ◽  
Induced Apoptosis

Background: Salinomycin, an ionophore antibiotic, is known to be an effective agent in reducing the viability of Glioblastoma (GBM) cells. The combination of salinomycin with other chemotherapeutic drugs would help to overcome the drug resistance of GBM cells. Objective: This study aims to test the combinatorial effect of salinomycin and AZD3463 in T98G GBM cells. Methods: The cytotoxic effects of drugs on T98G GBM cells were determined by using WST-8 assay. Flow cytometry was used to identify apoptosis and cell cycle profiles after treatments. Real-time PCR was used to portray mRNA expression profiles of genes in the Wnt-signaling pathway after treatments. Results: IC50 concentrations of AZD3463 and salinomycin were 529nM and 7.3μM for 48h, respectively. The combination concentrations of AZD3463 and salinomycin were 3.3μM and 333nM, respectively. The combination treatment showed a synergistic effect on reducing the viability of GBM cells. AZD3463, salinomycin, and their combination induced apoptosis in 1.2, 1.4, and 3.2 folds, respectively. AZD3463 and the combination treatment induced the cell cycle arrest at the G1 phase. Salinomycin and AZD3463 treatments, either alone or in combination, resulted in the downregulation or upregulation of mRNA expression levels of genes in the Wntsignaling pathway. Conclusion: Salinomycin, AZD3463, and their combination may inhibit proliferation and induce apoptosis in GBM cells due to a decrease in expression levels of genes acting in both the canonical and non-canonical Wnt signaling pathways. The Wnt signaling pathway may be involved in salinomycin-AZD3463 drug interaction.

scholarly journals Effects of icariin on long noncoding RNA and mRNA expression profile in the aortas of apoE-deficient mice

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Yibing Zhang ◽  
Rui Xu ◽  
Xiangjun Li ◽  
Qi Tan ◽  
Peng Huang ◽  
...  
Keyword(s):  
Mrna Expression ◽  
High Fat Diet ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Protective Mechanism ◽  
Beneficial Effects ◽  
Plaque Area ◽  
Kinase C ◽  
Global Signal ◽  
Deficient Mice

Abstract Objective : The beneficial effects of icariin (ICA) in ameliorating atherosclerosis (AS) are well known, but the underlying protective mechanism has not been fully elucidated. The present study aimed to investigate altered long noncosing RNA (lncRNA) and mRNA expression profiles in ApoE−/− mice after ICA treatment. Method : The atherosclerotic plaque area was evaluated on high-fat diet (HFD)-induced ApoE−/− mice treated with either ICA or vehicle. LncRNA and mRNA integrated microarrays was performed on aortic tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were utilized to explore the significant function and pathway of the differentially expressed (DE) mRNAs, global signal transduction network were constructed to select key mRNAs, and lncRNA–mRNA co-expression network was built to find out the interactions between lncRNA and mRNA. Quantitative real-time PCR (qPCR) was used to further validate the expressions of selected lncRNAs and mRNAs. Results : Administration of ICA significantly reduced plaque size after 12 weeks (P<0.05). A total of 1512 DE lncRNAs and 2059 DE mRNAs were identified. The mRNAs: protein kinase C, β (Prkcb), Cyp2c65, Mapk10, Calmodulin 5 (Calm5), Calmodulin-like 3 (Calml3) and Camk4 were selected as hub mRNAs, the correlated lncRNAs in co-expression network were identified as important regulatory lncRNAs. The identified target pairs such as lncRNA-NONMMUT000659/Prkcb may play critical roles in AS development mediated by ICA. Conclusion : Taken together, our study highlights a panel of DE lncRNAs and mRNAs that could explain the molecular mechanism of ICA’s anti-atherosclerotic effects. The work lays a foundation for subsequent genes functional researches, which could contribute to provide new therapeutic targets for AS.

scholarly journals Druggable Nucleolin Identifies Breast Tumours Associated with Poor Prognosis That Exhibit Different Biological Processes

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 390 ◽  
Author(s):  
Flora Nguyen Van Long ◽  
Audrey Lardy-Cleaud ◽  
Susan Bray ◽  
Sylvie Chabaud ◽  
Thierry Dubois ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Expression Profiles ◽  
Disease Free Survival ◽  
Mrna Levels ◽  
Breast Cancers ◽  
Breast Tumours ◽  
Expression Levels ◽  
Cancer Management ◽  
Mrna Expression Levels

Background: Nucleolin (NCL) is a multifunctional protein with oncogenic properties. Anti-NCL drugs show strong cytotoxic effects, including in triple-negative breast cancer (TNBC) models, and are currently being evaluated in phase II clinical trials. However, few studies have investigated the clinical value of NCL and whether NCL stratified cancer patients. Here, we have investigated for the first time the association of NCL with clinical characteristics in breast cancers independently of the different subtypes. Methods: Using two independent series (n = 216; n = 661), we evaluated the prognostic value of NCL in non-metastatic breast cancers using univariate and/or multivariate Cox-regression analyses. Results: We reported that NCL mRNA expression levels are markers of poor survivals independently of tumour size and lymph node invasion status (n = 216). In addition, an association of NCL expression levels with poor survival was observed in TNBC (n = 40, overall survival (OS) p = 0.0287, disease-free survival (DFS) p = 0.0194). Transcriptomic analyses issued from The Cancer Genome Atlas (TCGA) database (n = 661) revealed that breast tumours expressing either low or high NCL mRNA expression levels exhibit different gene expression profiles. These data suggest that tumours expressing high NCL mRNA levels are different from those expressing low NCL mRNA levels. Conclusions: NCL is an independent marker of prognosis in breast cancers. We anticipated that anti-NCL is a promising therapeutic strategy that could rapidly be evaluated in high NCL-expressing tumours to improve breast cancer management.

mRNA expression profiles in circulating tumor cells (CTCs) of patients with metastatic breast cancer (MBC) treated with aromatase inhibitors (AI).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11045-11045
Author(s):  
Esther Anneke Reijm ◽  
Anieta M. Sieuwerts ◽  
Joan Bolt-de Vries ◽  
Bianca Mostert ◽  
Wendy Onstenk ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Mrna Expression ◽  
Expression Profiles ◽  
Statistical Significance ◽  
Metastatic Breast ◽  
First Line ◽  
Primary Tumors ◽  
Cox Regression Analysis ◽  
Expression Levels ◽  
Poor Outcome

11045 Background: Enumeration of CTCs can be used to assess prognosis in MBC and to evaluate treatment response. Besides enumeration, molecular CTC characterization is a promising tool to develop a more personalized treatment approach. Here, we evaluated the association between mRNA expression of currently known CTC-specific genes and response to first-line AI in MBC patients with estrogen receptor (ER)+ primary tumors. Methods: CTCs were isolated and enumerated from blood of 25 MBC patients before first-line therapy with an AI. Fourteen patients received a non-steroidal AI (8 letrozole, 6 anastrozole) and 11 patients were treated with exemestane. mRNA expression levels of 96 genes were measured by quantitative RT-PCR as previously described (Sieuwerts et al. Clin Cancer Res. 17:3600-3618, 2011). Expression levels of these genes were studied for their association with time to progression (TTP) after start first-line AI. Results: Median TTP was 338 (range 14–1,239) days. Median baseline CTC count for the 25 patients was 14 (range 0–753). In this relatively small cohort, the clinically relevant cut-off level of ≥5 CTCs in association with TTP did not reach statistical significance (Hazard Ratio [HR] 4.76, 95% Confidence Interval [CI]: 0.59–38.22, P=0.14). For type of AI, when comparing steroidal with non-steroidal AI, the measures in Cox univariate regression analysis were HR 2.54 (95% CI: 0.67–9.64), P=0.17. A 10-gene CTC profile was constructed based on the Wald statistics of the contribution of the individual genes in univariate Cox regression analysis of TTP. To identify patients with good and poor outcome, the Wald corrected sum of the 10 genes was used to dichotomize the continuous 10-gene predictor (HR 12.87 [95% CI: 1.60–103.56], P=0.016). In multivariate analysis, corrected for the clinically relevant variables type of AI and CTC count, only the 10-gene CTC profile was an independent factor associated with TTP (HR 12.46 [95% CI: 1.29-120.08], P=0.029). Conclusions: A 10-gene CTC predictor was constructed which distinguishes good and poor outcome to first-line AI in MBC patients. This profile is currently being validated in an independent group of patients.

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