from The Online Transplant Center by Kenar D Jhaveri
A novel concept has been emerging in the last few years regarding micro RNAs. It already has reached some human data in transplant patients.
What is micro RNA? These are non coding areas of the RNA that play a critical role in regulation of gene expression. They might alter the structure and lead to either expression or regression of the protein in question.
There is mice data that microRNAs play a role in immune response, adaptive immunity, inflammation, fibrosis and epithelial changes. The role of microRNA will help us understand intracellular signalling, expression of proteins, modulation of cytokines, and graft response better.
Few simple examples are: miR 155 regulates immune response to bacterial infections and viral infections and helps in the crosstalk macrophage becoming an activated macrophage. Myeloid stem cell goes to becoming a mast cell due to miR 223; and so forth. [click to continue…]
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While it is clear now that microRNAs play an important regulatory role in nearly all areas of biology, what may be more interesting is the breath of function of just a single microRNA. It is estimated that microRNAs regulate up to 60% of all genes and some say that “each microRNA can target hundreds of genes” and “a single microRNA can regulate entire networks of genes”. So here is an interesting look at a single microRNA that has a far-reaching effect in many biological systems.
Several studies have demonstrated the functional role of microRNA-146a in the immune response. MicroRNA-146a feedback inhibits production in macrophages, is upregulated by HSV-1 infection, has been associated with proinflammatory signaling in stressed brain cells and Alzheimer’s disease (AD) brain, modulates CFH gene expression to regulate an inflammatory response, and plays a functional role in T lymphocyte-mediated immune response. These and other studies demonstrate the great potential for anti-miRNAs as an effective therapeutic strategy against pathogenic inflammatory signaling.
Additionally, there have been many reports describing microRNA-146a’s role in cancer. MicroRNA-146a suppresses prostate cancer transformation from androgen-dependent to -independent cells, suppresses a kinase coding gene which reduces cell proliferation, invasion, and metastasis to human bone marrow endothelial cell monolayers, and is dysregulated by latent membrane protein 1 (LMP1) which contributes substantially to the oncogenic potential of Epstein-Barr virus. It is projected that microRNA-146a and other microRNAs may one day become biomarkers for clinical diagnosis of several types of cancer.
- Curtale G, Citarella F, Carissimi C, Goldoni M, Carucci N, Fulci V, Franceschini D, Meloni F, Barnaba V, Macino G. (2010) An emerging player in the adaptive immune response: microRNA-146a is a modulator of IL-2 expression and activation-induced cell death in T lymphocytes. Blood 115(2), 265-73. [abstract]
- Hou J, Wang P, Lin L, Liu X, Ma F, An H, Wang Z, Cao X. (2009) MicroRNA-146a feedback inhibits RIG-I-dependent Type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. J Immunol 183(3), 2150-58. [abstract]
- Hill JM, Zhao Y, Clement C, Neumann DM, Lukiw WJ. (2009) HSV-1 infection of human brain cells induces miRNA-146a and Alzheimer-type inflammatory signaling. Neuroreport 20(16), 1500-505. [abstract]
- Lukiw WJ, Zhao Y, Cui JG. (2008) An NF-kappaB-sensitive micro RNA-146a-mediated inflammatory circuit in Alzheimer disease and in stressed human brain cells. J Biol Chem 283(46), 31315-22. [abstract]
- Cameron JE, Yin Q, Fewell C, Lacey M, McBride J, Wang X, Lin Z, Schaefer BC, Flemington EK. (2008) The Epstein-Barr Virus latent membrane protein 1 (LMP1) induces cellular microRNA-146a, a modulator of lymphocyte signaling pathways. J Virol 82(4), 1946-58. [abstract]
- Lin SL, Chiang A, Chang D, Ying SY. (2008) Loss of mir-146a function in hormone-refractory prostate cancer. RNA 14(3), 417-24. [abstract]
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Researchers at the LSU Neuroscience Center have discovered a role for miRNA-146a in the evasion of Herpes simplex virus type-1 (HSV-1) from the complement system (a major first-line host defense mechanism), and the activation of key elements of the arachidonic acid cascade known to contribute to Alzheimer-type neuropathological change.
MicroRNA microarray revealed that human primary neural cells infected with HSV-1 (17syn +) showed upregulation of miRNA-146a, a brain-enriched microRNA that is associated with proinflammatory signaling in stressed brain cells and Alzheimer’s disease.
Hill JM, Zhao Y, Clement C, Neumann DM, Lukiw WJ. (2009) HSV-1 infection of human brain cells induces miRNA-146a and Alzheimer-type inflammatory signaling. Neuroreport 20(16), 1500-505. [abstract]