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]