Genomes and Genes
Gene Symbol: Mir146
Description: microRNA 146
Alias: Mirn146, miR-146a, mmu-mir-146
- Zhao J, Rao D, Boldin M, Taganov K, O Connell R, Baltimore D. NF-kappaB dysregulation in microRNA-146a-deficient mice drives the development of myeloid malignancies. Proc Natl Acad Sci U S A. 2011;108:9184-9 pubmed publisher..Genetic ablation of NF-?B p50 suppresses the myeloproliferation, showing that dysregulation of NF-?B is responsible for the myeloproliferative disease. ..
- Etzrodt M, Cortez Retamozo V, Newton A, Zhao J, Ng A, Wildgruber M, et al. Regulation of monocyte functional heterogeneity by miR-146a and Relb. Cell Rep. 2012;1:317-24 pubmed
- Stickel N, Prinz G, Pfeifer D, Hasselblatt P, Schmitt Graeff A, Follo M, et al. MiR-146a regulates the TRAF6/TNF-axis in donor T cells during GVHD. Blood. 2014;124:2586-95 pubmed publisher..Because miR-146a expression can be exogenously enhanced, our results provide a novel targeted molecular approach to mitigate GVHD. ..
- Schulte L, Westermann A, Vogel J. Differential activation and functional specialization of miR-146 and miR-155 in innate immune sensing. Nucleic Acids Res. 2013;41:542-53 pubmed publisher..We predict that dose-dependent responses to environmental stimuli may involve functional specialization of seemingly co-induced miRNAs in other cellular circuitries as well. ..
- Huang C, Liu X, QunZhou -, Xie J, Ma T, Meng X, et al. MiR-146a modulates macrophage polarization by inhibiting Notch1 pathway in RAW264.7 macrophages. Int Immunopharmacol. 2016;32:46-54 pubmed publisher..Taken together, it was suggested that miR-146a might serve as a molecular regulator in macrophage polarization and is a potential therapeutic target for inflammatory diseases. ..
- Saba R, Gushue S, Huzarewich R, Manguiat K, Medina S, Robertson C, et al. MicroRNA 146a (miR-146a) is over-expressed during prion disease and modulates the innate immune response and the microglial activation state. PLoS ONE. 2012;7:e30832 pubmed publisher..Based on our results, we propose a role for miR-146a as a potent modulator of microglial function by regulating the activation state during prion induced neurodegeneration. ..
- Jiang W, Kong L, Ni Q, Lu Y, Ding W, Liu G, et al. miR-146a ameliorates liver ischemia/reperfusion injury by suppressing IRAK1 and TRAF6. PLoS ONE. 2014;9:e101530 pubmed publisher..We conclude that miR-146a ameliorates liver ischemia/reperfusion injury in vivo and hypoxia/reoxygenation injury in vitro by directly suppressing IRAK1 and TRAF6. ..
- Wu X, Yan T, Wang Z, Wu X, Cao G, Zhang C. BM-MSCs-derived microvesicles promote allogeneic kidney graft survival through enhancing micro-146a expression of dendritic cells. Immunol Lett. 2017;191:55-62 pubmed publisher..In summary, our data suggested that the BM-MSCs-derived MVs improved allogenic kidney transplantation survival through inhibiting DCs maturity by miR-146a. ..
- Santra M, Zhang Z, Yang J, Santra S, Santra S, Chopp M, et al. Thymosin ?4 up-regulation of microRNA-146a promotes oligodendrocyte differentiation and suppression of the Toll-like proinflammatory pathway. J Biol Chem. 2014;289:19508-18 pubmed publisher..Transfection of anti-miR-146a nucleotides reversed the inhibitory effect of T?4 on IRAK1 and TRAF6 and decreased expression of MBP. These data suggest that T?4 suppresses the TLR proinflammatory pathway by up-regulating miR-146a. ..
- Lindner J, Kayo H, Hedlund S, Fukuda Y, Fukao T, Nielsen P. Cutting edge: The transcription factor Bob1 counteracts B cell activation and regulates miR-146a in B cells. J Immunol. 2014;192:4483-6 pubmed publisher..The inability to restrict B cell signaling could contribute to the immunodeficient phenotype of these mice and is consistent with an important role for Bob1 in suppressing B cell activation in vivo. ..
- Pratama A, Srivastava M, Williams N, Papa I, Lee S, Dinh X, et al. MicroRNA-146a regulates ICOS-ICOSL signalling to limit accumulation of T follicular helper cells and germinal centres. Nat Commun. 2015;6:6436 pubmed publisher..Collectively, miR-146a emerges as a post-transcriptional brake to limit Tfh cells and GC responses. ..
- Guo Q, Zhang J, Li J, Zou L, Zhang J, Xie Z, et al. Forced miR-146a expression causes autoimmune lymphoproliferative syndrome in mice via downregulation of Fas in germinal center B cells. Blood. 2013;121:4875-83 pubmed publisher..These results indicate that miR-146a may be involved in the pathogenesis of ALPS by targeting Fas and may therefore serve as a novel therapeutic target. ..
- Liu R, Yi B, Wei S, Yang W, Hart K, Chauhan P, et al. FOXP3-miR-146-NF-ÎºB Axis and Therapy for Precancerous Lesions in Prostate. Cancer Res. 2015;75:1714-24 pubmed publisher..Our data suggest that the FOXP3-miR-146-NF-ÎºB axis has a functional role during tumor initiation in prostate cancer. Targeting the miR-146-NF-ÎºB axis may provide a new therapeutic approach for prostate cancers with FOXP3 defects. ..
- Mohr S, Doebele C, Comoglio F, Berg T, Beck J, Bohnenberger H, et al. Hoxa9 and Meis1 Cooperatively Induce Addiction to Syk Signaling by Suppressing miR-146a in Acute Myeloid Leukemia. Cancer Cell. 2017;31:549-562.e11 pubmed publisher..Finally, Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia. ..
- Huffaker T, Hu R, Runtsch M, Bake E, Chen X, Zhao J, et al. Epistasis between microRNAs 155 and 146a during T cell-mediated antitumor immunity. Cell Rep. 2012;2:1697-709 pubmed publisher..Our work reveals critical roles for miRNAs in the reciprocal regulation of CD4(+) and CD8(+) T cell-mediated antitumor immunity and demonstrates the dominant nature of miR-155 during its promotion of immune responses. ..
- Heggermont W, Papageorgiou A, Quaegebeur A, Deckx S, Carai P, Verhesen W, et al. Inhibition of MicroRNA-146a and Overexpression of Its Target Dihydrolipoyl Succinyltransferase Protect Against Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction. Circulation. 2017;136:747-761 pubmed publisher..Altogether we show that the microRNA-146a and its target DLST are important metabolic players in left ventricular dysfunction. ..
- Feng M, Shi F, Qiu C, Peng W. MicroRNA-181a, -146a and -146b in spleen CD4+ T lymphocytes play proinflammatory roles in a murine model of asthma. Int Immunopharmacol. 2012;13:347-53 pubmed publisher..These observations suggest that microRNA-181a, -146a and -146b are proinflammatory factors in asthma, and that down-regulation of miRNA-146a may partially account for the anti-inflammatory effect of dexamethasone. ..
- Cheng H, Besla R, Li A, Chen Z, Shikatani E, Nazari Jahantigh M, et al. Paradoxical Suppression of Atherosclerosis in the Absence of microRNA-146a. Circ Res. 2017;121:354-367 pubmed publisher..Our study reveals that miR-146a regulates cholesterol metabolism and tempers chronic inflammatory responses to atherogenic diet by restraining proinflammatory signaling in endothelial cells and BM-derived cells. ..
- Horie T, Ono K, Nishi H, Nagao K, Kinoshita M, Watanabe S, et al. Acute doxorubicin cardiotoxicity is associated with miR-146a-induced inhibition of the neuregulin-ErbB pathway. Cardiovasc Res. 2010;87:656-64 pubmed publisher..Inhibition of both ErbB2 and ErbB4 signalling may be one of the reasons why those patients who receive concurrent therapy with Dox and trastuzumab suffer from CHF. ..
- Jiang M, Xiang Y, Wang D, Gao J, Liu D, Liu Y, et al. Dysregulated expression of miR-146a contributes to age-related dysfunction of macrophages. Aging Cell. 2012;11:29-40 pubmed publisher..These data indicate that the dysregulated expression of miR-146a results in the age-associated dysfunction of macrophages, and miR-146a may be a good target for the treatment of age-related inflammatory diseases. ..
- Rudnicki A, Shivatzki S, Beyer L, Takada Y, Raphael Y, Avraham K. microRNA-224 regulates Pentraxin 3, a component of the humoral arm of innate immunity, in inner ear inflammation. Hum Mol Genet. 2014;23:3138-46 pubmed publisher..An understanding of the molecular components of the inflammatory pathway may help develop therapeutics for reducing inflammation associated with inner ear injury. ..
- Zago M, Rico De Souza A, Hecht E, Rousseau S, Hamid Q, Eidelman D, et al. The NF-?B family member RelB regulates microRNA miR-146a to suppress cigarette smoke-induced COX-2 protein expression in lung fibroblasts. Toxicol Lett. 2014;226:107-16 pubmed publisher..These data highlight the potential of a RelB-miR-146a axis as a novel regulatory pathway that attenuates inflammation in response to respiratory toxicants. ..
- Juhász K, Gombos K, Szirmai M, Revesz P, Magda I, Gocze K, et al. DMBA induces deregulation of miRNA expression of let-7, miR-21 and miR-146a in CBA/CA mice. In Vivo. 2012;26:113-7 pubmed..The altered micro-RNA expression can be regarded as an early effect of exposure to chemical carcinogens. To our knowledge, this is the first study of miRNA modulation caused by DMBA in non-malignant tissues. ..
- Bai Y, Qian C, Qian L, Ma F, Hou J, Chen Y, et al. Integrin CD11b negatively regulates TLR9-triggered dendritic cell cross-priming by upregulating microRNA-146a. J Immunol. 2012;188:5293-302 pubmed publisher..Our data indicate a new mechanism for the regulation of DC cross-priming through integrins and miRNAs. ..
- Butcher M, Filipowicz A, Waseem T, McGary C, Crow K, Magilnick N, et al. Atherosclerosis-Driven Treg Plasticity Results in Formation of a Dysfunctional Subset of Plastic IFN?+ Th1/Tregs. Circ Res. 2016;119:1190-1203 pubmed publisher..Atherosclerosis drives Treg plasticity, resulting in the accumulation of dysfunctional IFN?+ Th1/Tregs that may permit further arterial inflammation and atherogenesis. ..
- Otsuka M, Jing Q, Georgel P, New L, Chen J, Mols J, et al. Hypersusceptibility to vesicular stomatitis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression. Immunity. 2007;27:123-34 pubmed..Our data suggest that host miRNA can play a role in host interactions with viruses. ..
- Feng B, Chen S, McArthur K, Wu Y, Sen S, Ding Q, et al. miR-146a-Mediated extracellular matrix protein production in chronic diabetes complications. Diabetes. 2011;60:2975-84 pubmed publisher..These studies showed a novel, glucose-induced molecular mechanism in which miR-146a participates in the transcriptional circuitry regulating extracellular matrix protein production in diabetes. ..
- Wang G, Huang Y, Wang L, Zhang Y, Xu J, Zhou Y, et al. MicroRNA-146a suppresses ROCK1 allowing hyperphosphorylation of tau in Alzheimer's disease. Sci Rep. 2016;6:26697 pubmed publisher..Our in vitro and in vivo results confirm that dysregulation of microRNA-146a biogenesis contributes to tau hyperphosphorylation and AD pathogenesis, and inhibition of this microRNA could be a viable novel in vivo therapy for AD. ..
- Wang S, Zhang X, Ju Y, Zhao B, Yan X, Hu J, et al. MicroRNA-146a feedback suppresses T cell immune function by targeting Stat1 in patients with chronic hepatitis B. J Immunol. 2013;191:293-301 pubmed publisher..Therefore, our work demonstrates that miR-146a upregulation in CHB causes impaired T cell function, which may contribute to immune defects and immunopathogenesis during chronic viral infection. ..
- PÃ©rez GarcÃa E, Meza Sosa K, LÃ³pez Sevilla Y, Camacho Concha N, SÃ¡nchez N, PÃ©rez MartÃnez L, et al. Merlin negative regulation by miR-146a promotes cell transformation. Biochem Biophys Res Commun. 2015;468:594-600 pubmed publisher..Accordingly, stable miR-146a-transfectant cells formed tumors with metastatic capacity inÂ vivo. Together our results uncover miRNAs as yet another negative mechanism controlling Merlin tumor suppressor functions. ..
- Li F, Huang Y, Huang Y, Kuang Y, Wei Y, Xiang L, et al. MicroRNA-146a promotes IgE class switch in B cells via upregulating 14-3-3? expression. Mol Immunol. 2017;92:180-189 pubmed publisher..These results demonstrate that miR-146a enhances class switch and secretion of IgE in B cells by upregulating 14-3-3? expression, and suggest that miR-146a may be a potential target for asthma therapy. ..
- Mann M, Mehta A, Zhao J, Lee K, Marinov G, Garcia Flores Y, et al. An NF-?B-microRNA regulatory network tunes macrophage inflammatory responses. Nat Commun. 2017;8:851 pubmed publisher..Here the authors show that NF-?B signalling, miR-155 and miR-146a form a complex network of cross-regulations to control gene transcription in macrophages for modulating inflammatory responses. ..
- Runtsch M, Hu R, Alexander M, Wallace J, Kagele D, Petersen C, et al. MicroRNA-146a constrains multiple parameters of intestinal immunity and increases susceptibility to DSS colitis. Oncotarget. 2015;6:28556-72 pubmed..Taken together, our data describe a role for miR-146a in constraining intestinal barrier function, a process that alters gut homeostasis and enhances at least some forms of intestinal disease in mice. ..
- Araujo R, Santos J, Fernandes M, Dias F, Sousa H, Ribeiro J, et al. Expression profile of microRNA-146a along HPV-induced multistep carcinogenesis: a study in HPV16 transgenic mice. J Cancer Res Clin Oncol. 2018;144:241-248 pubmed publisher..Taken together, these data implicate and suggest different roles of miR-146a in HPV-mediated carcinogenesis. ..
- Cheng Y, Kuang W, Hao Y, Zhang D, Lei M, Du L, et al. Downregulation of miR-27a* and miR-532-5p and upregulation of miR-146a and miR-155 in LPS-induced RAW264.7 macrophage cells. Inflammation. 2012;35:1308-13 pubmed publisher..Our findings may provide the basic information for the precise roles of miRNAs in the macrophage inflammatory response to LPS stimulation in the future. ..
- Gauna A, Park Y, Nayar G, Onate M, Jin J, Stewart C, et al. Dysregulated co-stimulatory molecule expression in a SjÃ¶gren's syndrome mouse model with potential implications by microRNA-146a. Mol Immunol. 2015;68:606-16 pubmed publisher..Therefore, this study provides the first indication that salivary gland epithelial cells may be critically involved in SjS progression by altering CD86:CD80 protein ratio in response to miR-146a upregulation. ..
- Wu D, Cerutti C, López Ramírez M, Pryce G, King Robson J, Simpson J, et al. Brain endothelial miR-146a negatively modulates T-cell adhesion through repressing multiple targets to inhibit NF-ÎºB activation. J Cereb Blood Flow Metab. 2015;35:412-23 pubmed publisher..We propose brain endothelial miR-146a as an endogenous NF-ÎºB inhibitor in BECs associated with decreased leukocyte adhesion during neuroinflammation. ..
- Cannella D, Brenier Pinchart M, Braun L, van Rooyen J, Bougdour A, Bastien O, et al. miR-146a and miR-155 delineate a MicroRNA fingerprint associated with Toxoplasma persistence in the host brain. Cell Rep. 2014;6:928-37 pubmed publisher..Remarkably, we found that miR-146a deficiency led to better control of parasite burden in the gut and most likely of early parasite dissemination in the brain tissue, resulting in the long-term survival of mice. ..
- He Y, Sun X, Huang C, Long X, Lin X, Zhang L, et al. MiR-146a regulates IL-6 production in lipopolysaccharide-induced RAW264.7 macrophage cells by inhibiting Notch1. Inflammation. 2014;37:71-82 pubmed publisher..These results suggested that miR-146a may function as a novel feedback negative regulator to LPS-induced production of inflammatory cytokines, at least in part, via inhibiting the expression of Notch1. ..
- Jayadev S, Case A, Alajajian B, Eastman A, Moller T, Garden G. Presenilin 2 influences miR146 level and activity in microglia. J Neurochem. 2013;127:592-9 pubmed publisher..We identified miR146, a negative regulator of monocyte pro-inflammatory response, as constitutively down-regulated in PS2 KO microglia...
- Dai Y, Jia P, Fang Y, Liu H, Jiao X, He J, et al. miR-146a is essential for lipopolysaccharide (LPS)-induced cross-tolerance against kidney ischemia/reperfusion injury in mice. Sci Rep. 2016;6:27091 pubmed publisher..Taken together, our results identify that miR146a exerts a kidney protective effect through negative regulation of acute inflammatory response by suppressing NF-ÎºB activation and proinflammatory genes expression. ..
- Halkein J, Tabruyn S, Ricke Hoch M, Haghikia A, Nguyen N, Scherr M, et al. MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy. J Clin Invest. 2013;123:2143-54 pubmed publisher..These results demonstrate that miR-146a is a downstream-mediator of 16K PRL that could potentially serve as a biomarker and therapeutic target for PPCM. ..
- Sun T, Li X, Song H, Gao F, Zhou G, Li X, et al. MiR-146a Aggravates LPS-Induced Inflammatory Injury by Targeting CXCR4 in the Articular Chondrocytes. Cell Physiol Biochem. 2017;44:1282-1294 pubmed publisher..Overexpression of CXCR4 could attenuate the inflammatory injury. Our findings provided novel evidence which might be useful for further studies exploring therapeutic approaches for OA via targeting miR-146a. ..
- Lugli G, Larson J, Demars M, Smalheiser N. Primary microRNA precursor transcripts are localized at post-synaptic densities in adult mouse forebrain. J Neurochem. 2012;123:459-66 pubmed publisher..This study supports the notion that miRNA biogenesis occurs locally near synapses in a regulated fashion. ..
- Jiang S, Hu Y, Deng S, Deng J, Yu X, Huang G, et al. miR-146a regulates inflammatory cytokine production in Porphyromonas gingivalis lipopolysaccharide-stimulated B cells by targeting IRAK1 but not TRAF6. Biochim Biophys Acta Mol Basis Dis. 2018;1864:925-933 pubmed publisher..In summary, miR-146a inhibits inflammatory cytokine production in B cells through directly targeting IRAK1, suggesting a regulatory role of miR-146a in B cell-mediated periodontal inflammation. ..
- Liu H, Zhang A, Zhao N, Li X. Role of miR-146a in Enforcing Effect of Specific Immunotherapy on Allergic Rhinitis. Immunol Invest. 2016;45:1-10 pubmed publisher..In conclusion, miR-146a can enforce OVA-specific immunotherapy via inducing antigen-specific regulatory T cells. miR-146a may have therapeutic potential to be used in the immunotherapy of allergic diseases. ..
- Dorval V, Mandemakers W, Jolivette F, Coudert L, Mazroui R, De Strooper B, et al. Gene and MicroRNA transcriptome analysis of Parkinson's related LRRK2 mouse models. PLoS ONE. 2014;9:e85510 pubmed publisher..Our data thus set the stage for future investigations regarding LRRK2 function in PD development. ..
- Elsarraj H, Hong Y, Valdez K, Carletti M, Salah S, Raimo M, et al. A novel role of microRNA146b in promoting mammary alveolar progenitor cell maintenance. J Cell Sci. 2013;126:2446-58 pubmed publisher..Therefore, we conclude that during pregnancy miR146b is involved in luminal alveolar progenitor cell maintenance, at least partially, by regulating STAT3?. ..
- Perske C, Lahat N, Sheffy Levin S, Bitterman H, Hemmerlein B, Rahat M. Loss of inducible nitric oxide synthase expression in the mouse renal cell carcinoma cell line RENCA is mediated by microRNA miR-146a. Am J Pathol. 2010;177:2046-54 pubmed publisher..Thus, inhibiting miR-146a may render these tumor cells susceptible to therapeutic strategies, such as adoptive transfer of M1-activated macrophages. ..