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miRNA and Tim-3

Tim Kehl, Christina Backes, Fabian Kern, Tobias Fehlmann, Nicole Ludwig, Eckart Meese, Hans-Peter Lenhof, Andreas Keller
miRNAs are typically repressing gene expression by binding to the 3' UTR, leading to degradation of the mRNA. This process is dominated by the eight-base seed region of the miRNA. Further, miRNAs are known not only to target genes but also to target significant parts of pathways. A logical line of thoughts is: miRNAs with similar (seed) sequence target similar sets of genes and thus similar sets of pathways. By calculating similarity scores for all 3.25 million pairs of 2,550 human miRNAs, we found that this pattern frequently holds, while we also observed exceptions...
December 5, 2017: Oncotarget
Mirna Kaafarani, Christian Schroer, Tim Takken
BACKGROUND: Hemodynamic responses to exercise are used as markers of diagnosis for cardiac diseases, systolic blood pressure (SBP) especially. However, the reference values for SBP in children at peak exertion level are outdated. This study aimed to establish current reference values for SBP, rate pressure product (RPP), and circulatory power (CircP). METHODS: Data from children who previously underwent cardiopulmonary exercise testing were categorized as healthy (N = 184; age 12...
December 2017: Expert Review of Cardiovascular Therapy
Stinne R Greisen, Yan Yan, Aida S Hansen, Morten T Venø, Jens R Nyengaard, Søren K Moestrup, Malene Hvid, Gordon J Freeman, Jørgen Kjems, Bent Deleuran
INTRODUCTION: Extracellular vesicles (EVs) have been recognized as route of communication in the microenvironment. They transfer proteins and microRNAs (miRNAs) between cells, and possess immunoregulatory properties. However, their role in immune-mediated diseases remains to be elucidated. We hypothesized a role for EVs in the rheumatoid arthritis (RA) joint, potentially involving the development of T cell exhaustion and transfer of the co-inhibitory receptor programmed death 1 (PD-1)...
2017: Frontiers in Immunology
Jiao Yang, Ronghua Liu, Yuting Deng, Jiawen Qian, Zhou Lu, Yuedi Wang, Dan Zhang, Feifei Luo, Yiwei Chu
MiR-15a/16, a miRNA cluster located at chromosome 13q14, has been reported to act as an immune regulator in inflammatory disorders besides its aberrant expression in cancers. However, little is known about its regulation in tumor-infiltrating immune cells. In our study, using an orthotropic GL261 mouse glioma model, we found that miR-15a/16 deficiency in host inhibited tumor growth and prolonged mice survival, which might be associated with the accumulation of tumor-infiltrating CD8+ T cells. More importantly, tumor-infiltrating CD8+ T cells without miR-15a/16 showed lower expression of PD-1, Tim-3 and LAG-3, and stronger secretion of IFN-γ, IL-2 and TNF-α than WT tumor-infiltrating CD8+ T cells...
November 15, 2017: International Journal of Cancer. Journal International du Cancer
Christopher R Deig, Marc S Mendonca, Tim Lautenschlaeger
Lung cancer is the leading cause of cancer deaths worldwide, with smoking as the main risk factor. The use of low-dose computed tomography (LDCT) as a screening method has shown a 20% lung cancer specific mortality benefit; however, widespread implementation is estimated to add $1.3-$2.0 billion in annual national health care expenditures. Blood-based microRNAs (miRNAs) have been investigated in detail and found to be potentially useful biomarkers indicating the presence of lung cancer, especially when used as a companion test to LDCT...
March 2017: Radiation Research
Philipp Jakob, Tim Kacprowski, Sylvie Briand-Schumacher, Dik Heg, Roland Klingenberg, Barbara E Stähli, Milosz Jaguszewski, Nicolas Rodondi, David Nanchen, Lorenz Räber, Pierre Vogt, Francois Mach, Stephan Windecker, Uwe Völker, Christian M Matter, Thomas F Lüscher, Ulf Landmesser
Aims: MicroRNAs (miRNA) are important non-coding modulators controlling patterns of gene expression. However, profiling and validation of circulating miRNA levels related to adverse cardiovascular outcome has not been performed in patients with an acute coronary syndrome (ACS). Methods and results: In a multicentre, prospective ACS cohort, 1002 out of 2168 patients presented with ST-segment elevation myocardial infarction (STEMI). Sixty-three STEMI patients experienced an adjudicated major cardiovascular event (MACE, defined as cardiac death or recurrent myocardial infarction) within 1 year of follow-up...
February 14, 2017: European Heart Journal
Annette Vriens, Tim S Nawrot, Nelly D Saenen, Eline B Provost, Michal Kicinski, Wouter Lefebvre, Charlotte Vanpoucke, Jan Van Deun, Olivier De Wever, Karen Vrijens, Patrick De Boever, Michelle Plusquin
BACKGROUND: Ultrafine particles (<100 nm) are ubiquitous present in the air and may contribute to adverse cardiovascular effects. Exposure to air pollutants can alter miRNA expression, which can affect downstream signaling pathways. miRNAs are present both in the intracellular and extracellular environment. In adults, miR-222 and miR-146a were identified as associated with particulate matter exposure. However, there is little evidence of molecular effects of ambient air pollution in children...
July 26, 2016: Environmental Health: a Global Access Science Source
Yue Wang, Qian Cheng, Jing Liu, Min Dong
Leukemia stem cells (LSCs) play the major role in relapse of acute myeloid leukemia (AML). Recent evidence indicates that microvesicles (MVs) released from cancer stem cells can promote tumor growth and invasion. In this study, we investigated whether LSCs-released MVs (LMVs) can regulate the malignance of AML cells and whether overexpression of tumor suppressive microRNA (miR), miR34a, is able to interrupt this process. LSCs were transfected with miRNA control (miRCtrl) or miR34a mimic for producing LMVs, respectively, defined as LMVs(miRCtrl) and LMVs(miR34a)...
2016: Stem Cells International
Maria Tsamou, Karen Vrijens, Narjes Madhloum, Wouter Lefebvre, Charlotte Vanpoucke, Tim S Nawrot
Particulate matter (PM) exposure during in utero life may entail adverse health outcomes in later-life. Air pollution's adverse effects are known to alter gene expression profiles, which can be regulated by microRNAs (miRNAs). We investigate the potential influence of air pollution exposure in prenatal life on placental miRNA expression. Within the framework of the ENVIRONAGE birth cohort, we measured the expression of six candidate miRNAs in placental tissue from 210 mother-newborn pairs by qRT-PCR. Trimester-specific PM2...
April 22, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Azadeh Azizian, Ingo Epping, Frank Kramer, Peter Jo, Markus Bernhardt, Julia Kitz, Gabriela Salinas, Hendrik A Wolff, Marian Grade, Tim Beißbarth, B Michael Ghadimi, Jochen Gaedcke
BACKGROUND: Patients with locally advanced rectal cancer are treated with preoperative chemoradiotherapy followed by surgical resection. Despite similar clinical parameters (uT2-3, uN+) and standard therapy, patients' prognoses differ widely. A possible prediction of prognosis through microRNAs as biomarkers out of treatment-naïve biopsies would allow individualized therapy options. METHODS: Microarray analysis of 45 microdissected preoperative biopsies from patients with rectal cancer was performed to identify potential microRNAs to predict overall survival, disease-free survival, cancer-specific survival, distant-metastasis-free survival, tumor regression grade, or nodal stage...
April 15, 2016: International Journal of Molecular Sciences
Ou Wang, Guanxiang Liang, Tim A McAllister, Graham Plastow, Kim Stanford, Brent Selinger, Le Luo Guan
Super-shedder cattle are a major disseminator of E. coli O157:H7 into the environment, and the terminal rectum has been proposed as the primary E. coli O157:H7 colonization site. This study aimed to identify host factors that are associated with the super-shedding process by comparing transcriptomic profiles in rectal tissue collected from 5 super-shedder cattle and 4 non-shedder cattle using RNA-Seq. In total, 17,859 ± 354 genes and 399 ± 16 miRNAs were detected, and 11,773 genes were expressed in all animals...
2016: PloS One
Tijs Louwies, Caroline Vuegen, Luc Int Panis, Bianca Cox, Karen Vrijens, Tim S Nawrot, Patrick De Boever
INTRODUCTION: Air pollution, a risk factor for cardiovascular diseases, can exert its effects through the microcirculation. Retinal blood vessel width is considered a marker for microvascular health and is associated with short-term PM10 exposure. microRNAs are key regulators of complex biological processes in cardiovascular health and disease and miRNA expression can be affected by air pollution exposure. Studies investigating the effect of ambient air pollution exposure on miRNA expression in combination with an assessment of the microvasculature do not exist...
May 2016: Environmental Research
Helena Kelly, Tim Downing, Nina L Tuite, Terry J Smith, Michael J Kerin, Róisín M Dwyer, Eoin Clancy, Thomas Barry, Kate Reddington
INTRODUCTION: Micro RNAs (miRNAs) are a class of highly conserved small non-coding RNAs that play an important part in the post-transcriptional regulation of gene expression. A substantial number of miRNAs have been proposed as biomarkers for diseases. While reverse transcriptase Real-time PCR (RT-qPCR) is considered the gold standard for the evaluation and validation of miRNA biomarkers, small RNA sequencing is now routinely being adopted for the identification of dysregulated miRNAs...
2015: PloS One
Yong Q Cheng, Jun P Ren, Juan Zhao, Jia M Wang, Yun Zhou, Guang Y Li, Jonathan P Moorman, Zhi Q Yao
Host immune responses must be tightly regulated by an intricate balance between positive and negative signals while fighting pathogens; persistent pathogens may usurp these regulatory mechanisms to dampen host immunity to facilitate survival in vivo. Here we report that Tim-3, a negative signalling molecule expressed on monocytes and T cells, is up-regulated on natural killer (NK) cells in individuals chronically infected with hepatitis C virus (HCV). Additionally, the transcription factor T-bet was also found to be up-regulated and associated with Tim-3 expression in NK cells during chronic HCV infection...
August 2015: Immunology
Annabell Bischoff, Michaela Bayerlová, Michaela Strotbek, Simone Schmid, Tim Beissbarth, Monilola A Olayioye
BACKGROUND: The growth factor heregulin (HRG) potently stimulates epithelial cell survival and proliferation through the binding of its cognate receptor ErbB3 (also known as HER3). ErbB3-dependent signal transmission relies on the dimerization partner ErbB2, a receptor tyrosine kinase that is frequently overexpressed and/or amplified in breast cancer cells. Substantial evidence suggests that deregulated ErbB3 expression also contributes to the transformed phenotype of breast cancer cells...
January 29, 2015: Cell Communication and Signaling: CCS
Josue Moura Romao, Weiwu Jin, Maolong He, Tim McAllister, Le Luo Guan
BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs found to regulate several biological processes including adipogenesis. Understanding adipose tissue regulation is critical for beef cattle as fat is an important determinant of beef quality and nutrient value. This study analyzed the association between genomic context characteristics of miRNAs with their expression and function in bovine adipose tissue. Twenty-four subcutaneous adipose tissue biopsies were obtained from eight British-continental crossbred steers at 3 different time points...
2014: BMC Genomics
Wei Meng, Zhenqing Ye, Ri Cui, James Perry, Vaia Dedousi-Huebner, Alexander Huebner, Yao Wang, Bin Li, Stefano Volinia, Hiroshi Nakanishi, Taewan Kim, Sung-Suk Suh, Leona W Ayers, Patrick Ross, Carlo M Croce, Arnab Chakravarti, Victor X Jin, Tim Lautenschlaeger
PURPOSE: We conducted genome-wide miRNA-sequencing (miRNA-seq) in primary cancer tissue from patients of lung adenocarcinoma to identify markers for the presence of lymph node metastasis. EXPERIMENTAL DESIGN: Markers for lymph node metastasis identified by sequencing were validated in a separate cohort using quantitative PCR. After additional validation in the The Cancer Genome Atlas (TCGA) dataset, functional characterization studies were conducted in vitro. RESULTS: MiR-31 was upregulated in lung adenocarcinoma tissues from patients with lymph node metastases compared with those without lymph node metastases...
October 1, 2013: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Martin A Rivas, Leandro Venturutti, Yi-Wen Huang, Roxana Schillaci, Tim Hui-Ming Huang, Patricia V Elizalde
INTRODUCTION: Experimental and clinical evidence points to a critical role of progesterone and the nuclear progesterone receptor (PR) in controlling mammary gland tumorigenesis. However, the molecular mechanisms of progesterone action in breast cancer still remain elusive. On the other hand, micro RNAs (miRNAs) are short ribonucleic acids which have also been found to play a pivotal role in cancer pathogenesis. The role of miRNA in progestin-induced breast cancer is poorly explored. In this study we explored progestin modulation of miRNA expression in mammary tumorigenesis...
2012: Breast Cancer Research: BCR
Tao Chen, Tim D Williams, Angela Mally, Carolin Hamberger, Leda Mirbahai, Kevin Hickling, J Kevin Chipman
Furan, a widely used industrial compound, has been found in a number of heated food items. Furan is carcinogenic to rats and mice, but the mechanism behind its carcinogenic effect is still not well understood. In this study, we tested the hypothesis that alteration of gene expression relating to cell cycle, apoptosis, DNA damage and of epigenetic modifications including miRNA and DNA methylation may contribute to rodent carcinogenicity of furan. Using quantitative PCR arrays specific to cell cycle-, apoptosis- and DNA damage-related genes, we found that three months furan treatment at 30 mg/kg (5 daily doses per week) induced extensive mRNA expression changes (largely up-regulation) in male Sprague Dawley rat liver, and the gene expression changes did not fully recover after a one month withdrawal of furan...
February 26, 2012: Toxicology
Wing Pui Tsang, Tim Tak Kwok
MicroRNAs (miRNA) are endogenously expressed non-coding RNAs that regulate gene expression post-transcriptionally. Let-7a miRNA is a founding member in the let-7 family and its down-regulation in association with over-expression of RAS and HMGA2 oncogenes has previously been reported. In the present study, caspase-3, the executioner caspase, was confirmed to be the target of let-7a as ectopic expression of let-7a decreased the luciferase activity of a reporter construct containing the 3' untranslated region of caspase-3 and at the same time repressed the enzyme expression in human squamous carcinoma A431 cells and hepatocellular carcinoma HepG2 cells...
October 2008: Apoptosis: An International Journal on Programmed Cell Death
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