MicroRNA‐146a and Human Disease

MicroRNAs (MiRNAs) belong to a class of small non‐coding regulatory RNAs that act through repression of protein expression at post‐transcriptional level and emerge to play important roles in many physiological and pathophysiological processes. MiR‐146a is a miRNA supposed to regulate innate immune, inflammatory response and antiviral pathway negatively. In this review, we focus on the recent progress in functional role of miR‐146a in innate immune, inflammatory response, virus infection and human diseases. Together, these findings indicate that manipulation of miR‐146a expression may represent a potential new therapy for several human diseases. Potential use of miR‐146a as a biomarker for disease diagnosis, prevention and treatment is also discussed.

[1]  Hao Wu,et al.  Distinct molecular mechanism for initiating TRAF6 signalling , 2002, Nature.

[2]  Isaac S. Kohane,et al.  Distinctive patterns of microRNA expression in primary muscular disorders , 2007, Proceedings of the National Academy of Sciences.

[3]  Jian-Rong Yang,et al.  A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. , 2008, Carcinogenesis.

[4]  J. Inoue,et al.  NF-kappaB activation in development and progression of cancer. , 2007, Cancer science.

[5]  C. Croce,et al.  The role of microRNA genes in papillary thyroid carcinoma. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[6]  P. Tam.  Faculty Opinions recommendation of miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. , 2009 .

[7]  Zhaohui Huang,et al.  Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer , 2010, International journal of cancer.

[8]  Y. Duan,et al.  Cyclic stretch induced miR-146a upregulation delays C2C12 myogenic differentiation through inhibition of Numb. , 2009, Biochemical and biophysical research communications.

[9]  Kaleb M. Pauley,et al.  Contrast in aberrant microRNA expression in systemic lupus erythematosus and rheumatoid arthritis: is microRNA-146 all we need? , 2009, Arthritis and rheumatism.

[10]  C. Birchmeier,et al.  Notch Function in Myogenesis , 2007, Cell cycle.

[11]  Chaoqian Xu,et al.  The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2 , 2011, Nature Medicine.

[12]  D. Banerjee,et al.  MiRSNPs or MiR-polymorphisms, new players in microRNA mediated regulation of the cell: Introducing microRNA pharmacogenomics , 2008, Cell cycle.

[13]  C. Croce,et al.  MicroRNA-133 controls cardiac hypertrophy , 2007, Nature Medicine.

[14]  Jaekyu Shin,et al.  Pharmacogenetics: from discovery to patient care. , 2009, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[15]  A. Kasprzyk,et al.  Narrowing and genomic annotation of the commonly deleted region of the 5q- syndrome. , 2002, Blood.

[16]  Hua Zhao,et al.  A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. , 2008, Carcinogenesis.

[17]  D. Banerjee,et al.  A miR-24 microRNA binding-site polymorphism in dihydrofolate reductase gene leads to methotrexate resistance , 2007, Proceedings of the National Academy of Sciences.

[18]  Pin Wang,et al.  MicroRNA-146a Feedback Inhibits RIG-I-Dependent Type I IFN Production in Macrophages by Targeting TRAF6, IRAK1, and IRAK21 , 2009, The Journal of Immunology.

[19]  Kedar S Vaidya,et al.  Breast cancer metastasis suppressor 1 up-regulates miR-146, which suppresses breast cancer metastasis. , 2009, Cancer research.

[20]  J. Bertino,et al.  MicroRNA polymorphisms: the future of pharmacogenomics, molecular epidemiology and individualized medicine. , 2009, Pharmacogenomics.

[21]  M. Lindsay,et al.  Rapid Changes in MicroRNA-146a Expression Negatively Regulate the IL-1β-Induced Inflammatory Response in Human Lung Alveolar Epithelial Cells1 , 2008, The Journal of Immunology.

[22]  Ryan D. Morin,et al.  Identification of miR-145 and miR-146a as mediators of the 5q– syndrome phenotype , 2010, Nature Medicine.

[23]  A. Whitehead,et al.  IL-1 Signaling Cascade in Liver Cells and the Involvement of a Soluble Form of the IL-1 Receptor Accessory Protein1 2 , 2000, The Journal of Immunology.

[24]  X. Chen,et al.  Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases , 2008, Cell Research.

[25]  O. Hermine,et al.  Deregulation of microRNA involved in hematopoiesis and the immune response in HTLV-I adult T-cell leukemia. , 2009, Blood.

[26]  P. Tak,et al.  MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. , 2009, Arthritis and rheumatism.

[27]  S. Fedele,et al.  MicroRNAs and ischemic heart disease: towards a better comprehension of pathogenesis, new diagnostic tools and new therapeutic targets. , 2009, Recent patents on cardiovascular drug discovery.

[28]  Liang-Hu Qu,et al.  MicroRNA Patterns Associated with Clinical Prognostic Parameters and CNS Relapse Prediction in Pediatric Acute Leukemia , 2009, PloS one.

[29]  J. Inoue,et al.  NF‐κB activation in development and progression of cancer , 2007 .

[30]  D. Baltimore,et al.  NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses , 2006, Proceedings of the National Academy of Sciences.

[31]  Ulus Atasoy,et al.  Circulating microRNAs in breast cancer and healthy subjects , 2009, BMC Research Notes.

[32]  V. Ambros.  The functions of animal microRNAs , 2004, Nature.

[33]  M. Lindsay,et al.  microRNAs and the immune response. , 2008, Trends in immunology.

[34]  J. Mrázek,et al.  Epstein-Barr Virus-Encoded Latent Membrane Protein 1 (LMP1) Induces the Expression of the Cellular MicroRNA miR-146a , 2007, RNA biology.

[35]  Shizuo Akira,et al.  The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses , 2004, Nature Immunology.

[36]  Keiichiro Nishida,et al.  Expression of microRNA-146 in rheumatoid arthritis synovial tissue. , 2008, Arthritis and rheumatism.

[37]  Michael Detmar,et al.  Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. , 2008, Arthritis and rheumatism.

[38]  M. Lindsay,et al.  Role of miRNA-146a in the regulation of the innate immune response and cancer. , 2008, Biochemical Society transactions.

[39]  Kaleb M. Pauley,et al.  miR-146a Is Critical for Endotoxin-induced Tolerance , 2009, The Journal of Biological Chemistry.

[40]  N. S. Asli,et al.  MicroRNAs in organogenesis and disease. , 2008, Current molecular medicine.

[41]  Stefano Volinia,et al.  Interferon modulation of cellular microRNAs as an antiviral mechanism , 2007, Nature.

[42]  S. Schokrpur,et al.  Expression of microRNA-146 suppresses NF-κB activity with reduction of metastatic potential in breast cancer cells , 2008, Oncogene.

[43]  Zhen Lin,et al.  Epstein-Barr Virus Latent Membrane Protein 1 Induces Cellular MicroRNA miR-146a, a Modulator of Lymphocyte Signaling Pathways , 2007, Journal of Virology.

[44]  Walter J. Lukiw,et al.  An NF-κB-sensitive Micro RNA-146a-mediated Inflammatory Circuit in Alzheimer Disease and in Stressed Human Brain Cells* , 2008, Journal of Biological Chemistry.

[45]  Wei Zhang,et al.  A functional polymorphism in Pre‐miR‐146a gene is associated with prostate cancer risk and mature miR‐146a expression in vivo , 2010, The Prostate.

[46]  Osamu Takeuchi,et al.  MDA5/RIG-I and virus recognition. , 2008, Current opinion in immunology.

[47]  A. Pivarcsi,et al.  MicroRNAs: novel regulators in skin inflammation , 2008, Clinical and experimental dermatology.

[48]  T. Rando,et al.  The regulation of Notch signaling in muscle stem cell activation and postnatal myogenesis. , 2005, Seminars in cell & developmental biology.

[49]  L. Young,et al.  Epstein–Barr virus and oncogenesis: from latent genes to tumours , 2003, Oncogene.

[50]  Haifan Lin,et al.  MicroRNAs: key regulators of stem cells , 2009, Nature Reviews Molecular Cell Biology.

[51]  Kaleb M. Pauley,et al.  Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients , 2008, Arthritis research & therapy.

[52]  Barbara Jarzab,et al.  Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma , 2008, Proceedings of the National Academy of Sciences.

[53]  O. Crasta,et al.  Suppression of LPS-induced Interferon-gamma and nitric oxide in splenic lymphocytes by select estrogen-regulated microRNAs: a novel mechanism of immune modulation. , 2008, Blood.

[54]  N. Rajewsky,et al.  A pancreatic islet-specific microRNA regulates insulin secretion , 2004, Nature.