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Microrna and purinergic receptor

Yiao Tan, Tengyue Zhang, Linyu Zhou, Shuhan Liu, Chaozhao Liang
BACKGROUND Chemoresistance is a main limitation in chemotherapy for therapeutic cancer. MicroRNA (miRNA) has been indicated in the progression and tumorigenesis of many types of cancer, but the effect of miR-34b-3p in bladder cancer (BCa) cells is still unknown. MATERIAL AND METHODS This research compared the multidrug-sensitive (5637) BCa cell line and the multidrug-resistant (EJ) BCa cell line. We found that CCND2 (G1/S-specific cyclin-D2) and P2RY1 (purinergic receptor P2Y1) were the targets of miR-34b-3p, as further validated by qRT-PCR (quantitative real-time polymerase chain reaction) and western blot analysis...
February 19, 2019: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Andrea Vereczkei, Omar Abdul-Rahman, Zsuzsa Halmai, Geza Nagy, Anna Szekely, Aniko Somogyi, Gabor Faludi, Zsofia Nemoda
INTRODUCTION: The activation of the ATP-gated P2RX7 (purinergic receptor P2X, ligand-gated ion channel, 7) produces microglial activation, a process which has been demonstrated in depression, bipolar disorder, and schizophrenia. Emerging data over the last years highlighted the importance of P2X7 cation channel as a potential drug target for these central nervous system disorders. The Gln460Arg (rs2230912) polymorphism of the P2RX7 gene has been widely studied in mood disorders, however the results are still controversial...
January 18, 2019: Progress in Neuro-psychopharmacology & Biological Psychiatry
Eva M Jimenez-Mateos, Jonathon Smith, Annette Nicke, Tobias Engel
Because of its prominent role in driving inflammatory processes, the ATP-gated purinergic P2 × 7 receptor has attracted much attention over the past decade as a potential therapeutic target for numerous human conditions, particularly diseases of the central nervous system, including neurodegenerative diseases (e.g. Alzheimer's and Huntington's disease), psychiatric disorders (e.g. schizophrenia and depression) and the neurological disease, epilepsy. Evidence stems from studies using experimental models and patient tissue showing changes in P2 × 7 expression and function under pathological conditions and beneficial effects provided by P2 × 7 antagonism...
December 26, 2018: Brain Research Bulletin
Wei Zhang, Biao Zhong, Chi Zhang, Congfeng Luo, Yulin Zhan
Inflammatory cytokines commonly initiate extreme changes in the synovium and cartilage microenvironment of osteoarthritis (OA) patients, which subsequently cause cellular dysfunction, especially in chondrocytes. It has been reported that induction of the purinergic P2X7 receptor (P2X7R) can regulate the expression of a variety of inflammatory factors, including interleukin (IL)-6 and -8, leading to OA pathogenesis. However, knowledge of the mechanism of upregulation of P2X7R in OA is still incomplete, and its role in chondrocyte proliferation is also not clear...
March 2018: FEBS Open Bio
Rilong Jin, Miaoda Shen, Liedao Yu, Xuanwei Wang, Xiangjin Lin
Adipose-derived stem cells (ADSCs) were previously considered to have an anti-inflammatory effect, and Interleukin-1β (IL-1β) was found to be a pro-inflammatory factor in chondrocytes, but the mechanism underlying ADSCs and IL-1β is unclear. In this study, we investigate whether P2X7 receptor (P2X7R) signalling, regulated by microRNA 373 (miR-373), was involved in the ADSCs and IL-1β mediated inflammation in osteoarthritis (OA). Chondrocytes were collected from 20 OA patients and 20 control participants, and ADSCs were collected from patients who had undergone abdominal surgery...
March 2017: Molecules and Cells
Shunmin Wang, Lujun Tang, Qian Zhou, Duomei Lu, Wulei Duan, Cheng Chen, Lu Huang, Yuansheng Tan
The abnormal proliferation and apoptosis of human aortic vascular smooth muscle cells (HAVSMCs) play an important role in the pathogenesis of hypertension. Recent study revealed that angiotensin II (Ang II) could elicit HAVSMC dysfunction, to induce or aggravate hypertension. Purinergic receptor P2Y6, an inflammation-inducible G protein-coupled receptor, promoted Ang II-induced hypertension. In the present study, we revealed that Ang II induced HAVSMC proliferation and upregulated P2Y6 protein levels. After knockdown of P2Y6, the promotive effect of Ang II on HAVSMC proliferation was restored...
May 2017: DNA and Cell Biology
Chiara Parisi, Giulia Napoli, Pablo Pelegrin, Cinzia Volonté
Amyotrophic lateral sclerosis (ALS) is a most frequently occurring and severe form of motor neuron disease, causing death within 3-5 years from diagnosis and with a worldwide incidence of about 2 per 100,000 person-years. Mutations in over twenty genes associated with familial forms of ALS have provided insights into the mechanisms leading to motor neuron death. Moreover, mutations in two RNA binding proteins, TAR DNA binding protein 43 and fused in sarcoma, have raised the intriguing possibility that perturbations of RNA metabolism, including that of the small endogenous RNA molecules that repress target genes at the posttranscriptional level, that is, microRNAs, may contribute to disease pathogenesis...
2016: Mediators of Inflammation
Tobias Engel, Gary P Brennan, Amaya Sanz-Rodriguez, Mariana Alves, Edward Beamer, Orla Watters, David C Henshall, Eva M Jimenez-Mateos
Cells have developed complex transcriptional regulatory mechanisms to maintain intracellular homeostasis and withstand pathophysiological stressors. Feed-forward loops comprising transcription factors that drive expression of both target gene and a microRNA as negative regulator, are gaining increasing recognition as key regulatory elements of cellular homeostasis. The ATP-gated purinergic P2X7 receptor (P2X7R) is an important driver of inflammation and has been implicated in the pathogenesis of numerous brain diseases including epilepsy...
February 2017: Biochimica et biophysica acta. Molecular cell research
Davide Ferrari, Nicoletta Bianchi, Holger K Eltzschig, Roberto Gambari
MicroRNAs (miRNAs) are small non-coding RNA molecules capable of silencing mRNA targets. miRNA dysregulation has been linked to cancer development, cardiovascular and neurological diseases, lipid metabolism, and impaired immunity. Therefore, miRNAs are gaining interest as putative novel disease biomarkers and therapeutic targets. Recent studies have shown that purinergic surface receptors activated by extracellular nucleotides (ATP, ADP, UTP, UDP), and by nucleosides such as adenosine (ADO), are subject to miRNA regulation...
October 2016: Trends in Molecular Medicine
Thomas Theis, Myung Yoo, Christopher S Park, Jian Chen, Sebastian Kügler, Kurt M Gibbs, Melitta Schachner
Based on the observation that microRNA (miRNA) 133b enhances regeneration after spinal cord injury in the adult zebrafish, we investigated whether this miRNA would be beneficial in a mammalian system in vitro and in vivo. We found that infection of cultured neurons with miR-133b promotes neurite outgrowth in vitro on an inhibitory substrate consisting of mixed chondroitin sulfate proteoglycans, when compared to infection with green fluorescent protein (GFP) for control. In vivo, viral infection of the injured adult mouse spinal cord at the time of injury at and in the vicinity of the lesion site enhanced expression of miR-133b...
August 2017: Molecular Neurobiology
Francesca Amoroso, Erica Salaro, Simonetta Falzoni, Paola Chiozzi, Anna Lisa Giuliani, Giorgio Cavallesco, Pio Maniscalco, Andrea Puozzo, Ilaria Bononi, Fernanda Martini, Mauro Tognon, Francesco Di Virgilio
Malignant pleural mesothelioma (MPM) is an aggressive tumor refractory to anti-blastic therapy. MPM cells show several genetic and biochemical defects, e.g. overexpression of oncogenes, downregulation of onco-suppressor genes, dysregulation of microRNA, or alteration of intracellular Ca2+ homeostasis and of apoptosis. No information is as yet available on purinergic signalling in this tumor. Signalling via the P2X7 (P2RX7 or P2X7R) purinergic receptor is attracting increasing attention as a pathway involved in cancer cell death or proliferation...
August 2, 2016: Oncotarget
C Parisi, G Napoli, S Amadio, A Spalloni, S Apolloni, P Longone, C Volonté
Understanding the means by which microglia self-regulate the neuroinflammatory response helps modulating their reaction during neurodegeneration. In amyotrophic lateral sclerosis (ALS), classical NF-κB pathway is related to persistent microglia activation and motor neuron injury; however, mechanisms of negative control of NF-κB activity remain unexplored. One of the major players in the termination of classical NF-κB pathway is the ubiquitin-editing enzyme A20, which has recognized anti-inflammatory functions...
March 2016: Cell Death and Differentiation
Rui Shi, Xin Zhou, Wen-Jie Ji, Ying-Ying Zhang, Yong-Qiang Ma, Jian-Qi Zhang, Yu-Ming Li
Platelets are anuclear cells and are devoid of genomic DNA, but they are capable of de novo protein synthesis from mRNA derived from their progenitor cells, megakaryocytes. There is mounting evidence that microRNA (miRNA) plays an important role in regulating gene expression in platelets. miR-223 is the most abundant miRNAs in megakaryocytes and platelets. One of the miR-223-regulated genes is ADP P2Y12, a key target for current antiplatelet drug therapy. Recent studies showed that a blunted response to P2Y12 antagonist, that is, high on-treatment platelet reactivity (HTPR), is a strong predictor of major cardiovascular events (MACEs) in coronary heart disease (CHD) patients receiving antiplatelet treatment...
2015: BioMed Research International
Olof Gidlöf, Ramasri Sathanoori, Marco Magistri, Mohammad Ali Faghihi, Claes Wahlestedt, Björn Olde, David Erlinge
Adenosine and uridine triphosphate (ATP and UTP) can act as extracellular signalling molecules, playing important roles in vascular biology and disease. ATP and UTP acting via the P2Y2-receptor have, for example, been shown to regulate endothelial dilatation, inflammation and angiogenesis. MicroRNAs (miRNAs), a class of regulatory, short, non-coding RNAs, have been shown to be important regulators of these biological processes. In this study, we used RNA deep-sequencing to explore changes in miRNA expression in the human microvascular endothelial cell line HMEC-1 upon UTP treatment...
2015: Journal of Vascular Research
F Cortinas-Elizondo, S von Gunten
No abstract text is available yet for this article.
September 2015: Allergy
Sophia Chen, Benjamin A H Smith, Joseena Iype, Alessandro Prestipino, Dietmar Pfeifer, Sebastian Grundmann, Annette Schmitt-Graeff, Marco Idzko, Yvonne Beck, Gabriele Prinz, Jürgen Finke, Justus Duyster, Robert Zeiser
The successful treatment of acute leukemias with allogeneic hematopoietic cell transplantation (allo-HCT) is limited by acute graft-versus-host disease (GVHD). Because microRNA-155 (miR-155) regulates activation of the innate immune system, we aimed to determine its function in dendritic cells (DCs) during GVHD in an experimental model. We observed that miR-155 deficiency of the recipient led to improved survival, reduced serum levels of proinflammatory cytokines, and lower GVHD histopathology scores. In addition, miR-155(-/-) bone marrow chimeric mice receiving allo-HCT and miR-155(-/-) DCs showed that miR-155 deficiency in the DC compartment was responsible for protection from GVHD...
July 2, 2015: Blood
A Zech, C K Ayata, F Pankratz, A Meyer, K Baudiß, S Cicko, G G Yegutkin, S Grundmann, M Idzko
BACKGROUND: Dendritic cells (DCs) are the professional antigen-presenting cells (APCs) in the lung. They are known to be key players in the induction and maintenance of allergic asthma by cross-linking innate and adaptive immune responses. MicroRNAs (miRNAs) are known to influence cell fate and function by translational suppression or induction of messenger RNA (mRNA) degradation. miR-155 has been shown to be a crucial regulator of the immune system. However, its function in the pathogenesis of allergic airway inflammation (AAI) is not completely elucidated yet...
September 2015: Allergy
Yaoping Tang, Yongchao Wang, Kyoung-Mi Park, Qiuping Hu, Jian-Peng Teoh, Zuzana Broskova, Punithavathi Ranganathan, Calpurnia Jayakumar, Jie Li, Huabo Su, Yaoliang Tang, Ganesan Ramesh, Il-Man Kim
AIMS: Cardiac injury is accompanied by dynamic changes in the expression of microRNAs (miRs). For example, miR-150 is down-regulated in patients with acute myocardial infarction, atrial fibrillation, dilated and ischaemic cardiomyopathy as well as in various mouse heart failure (HF) models. Circulating miR-150 has been recently proposed as a better biomarker of HF than traditional clinical markers such as brain natriuretic peptide. We recently showed using the β-arrestin-biased β-blocker, carvedilol that β-arrestin1-biased β1-adrenergic receptor cardioprotective signalling stimulates the processing of miR-150 in the heart...
June 1, 2015: Cardiovascular Research
O Monfredi, M R Boyett
Sick sinus syndrome remains a highly relevant clinical entity, being responsible for the implantation of the majority of electronic pacemakers worldwide. It is an infinitely more complex disease than it was believed when first described in the mid part of the 20th century. It not only involves the innate leading pacemaker region of the heart, the sinoatrial node, but also the atrial myocardium, predisposing to atrial tachydysrhythmias. It remains controversial as to whether the dysfunction of the sinoatrial node directly causes the dysfunction of the atrial myocardium, or vice versa, or indeed whether these two aspects of the condition arise through some related underlying pathological mechanism, such as extracellular matrix remodeling, i...
June 2015: Journal of Molecular and Cellular Cardiology
Luming Zheng, Xukui Zhang, Feng Yang, Jian Zhu, Peng Zhou, Fang Yu, Lei Hou, Lei Xiao, Qingqing He, Baocheng Wang
Breast cancer is the most common cancer in women around the world. However, the molecular mechanisms underlying breast cancer pathogenesis are only partially understood. Here, in this study, we found that P2X7R was up-regulated and miR-216b was down-regulated in breast cancer cell lines and tissues. Using bioinformatic analysis and 3'UTR luciferase reporter assay, we determined P2X7R can be directly targeted by miR-216b, which can down-regulate endogenous P2X7R mRNA and protein levels. Ectopic expression of miR-216b mimics leads to inhibited cell growth and apoptosis, while blocking expression of the miR-216b results in increased cell proliferation...
September 12, 2014: Biochemical and Biophysical Research Communications
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