Editing MicroRNA (section)

====Alcoholism====
The vital role of miRNAs in gene expression is significant to [[addiction]], specifically [[alcoholism]].<ref name="Lewohl">{{cite journal | vauthors = Lewohl JM, Nunez YO, Dodd PR, Tiwari GR, Harris RA, Mayfield RD | title = Up-regulation of microRNAs in brain of human alcoholics | journal = Alcoholism: Clinical and Experimental Research | volume = 35 | issue = 11 | pages = 1928–37 | date = November 2011 | pmid = 21651580 | pmc = 3170679 | doi = 10.1111/j.1530-0277.2011.01544.x }}</ref> Chronic alcohol abuse results in persistent changes in brain function mediated in part by alterations in [[gene expression]].<ref name="Lewohl" /> miRNA global regulation of many downstream genes deems significant regarding the reorganization or synaptic connections or long term neural adaptations involving the behavioral change from alcohol consumption to [[alcohol withdrawal syndrome|withdrawal]] and/or [[Alcohol dependence|dependence]].<ref name="Tapocik1">{{cite journal | vauthors = Tapocik JD, Solomon M, Flanigan M, Meinhardt M, Barbier E, Schank JR, Schwandt M, Sommer WH, Heilig M | title = Coordinated dysregulation of mRNAs and microRNAs in the rat medial prefrontal cortex following a history of alcohol dependence | journal = The Pharmacogenomics Journal | volume = 13 | issue = 3 | pages = 286–96 | date = June 2013 | pmid = 22614244 | pmc = 3546132 | doi = 10.1038/tpj.2012.17 }}</ref> Up to 35 different miRNAs have been found to be altered in the alcoholic post-mortem brain, all of which target genes that include the regulation of the [[cell cycle]], [[apoptosis]], [[cell adhesion]], [[neural development|nervous system development]] and [[cell signaling]].<ref name="Lewohl" /> Altered miRNA levels were found in the medial [[prefrontal cortex]] of alcohol-dependent mice, suggesting the role of miRNA in orchestrating translational imbalances and the creation of differentially expressed proteins within an area of the brain where complex cognitive behavior and [[decision making]] likely originate.<ref name="Gorini">{{cite journal | vauthors = Gorini G, Nunez YO, Mayfield RD | title = Integration of miRNA and protein profiling reveals coordinated neuroadaptations in the alcohol-dependent mouse brain | journal = PLOS ONE | volume = 8 | issue = 12 | pages = e82565 | year = 2013 | pmid = 24358208 | pmc = 3865091 | doi = 10.1371/journal.pone.0082565 | bibcode = 2013PLoSO...882565G | doi-access = free }}</ref>

miRNAs can be either upregulated or downregulated in response to chronic alcohol use. [[miR-206]] expression increased in the prefrontal cortex of alcohol-dependent rats, targeting the transcription factor brain-derived neurotrophic factor ([[BDNF]]) and ultimately reducing its expression. BDNF plays a critical role in the formation and maturation of new neurons and synapses, suggesting a possible implication in synapse growth/[[synaptic plasticity]] in alcohol abusers.<ref name="Tapocik2">{{cite journal | vauthors = Tapocik JD, Barbier E, Flanigan M, Solomon M, Pincus A, Pilling A, Sun H, Schank JR, King C, Heilig M | title = microRNA-206 in rat medial prefrontal cortex regulates BDNF expression and alcohol drinking | journal = The Journal of Neuroscience | volume = 34 | issue = 13 | pages = 4581–88 | date = March 2014 | pmid = 24672003 | pmc = 3965783 | doi = 10.1523/JNEUROSCI.0445-14.2014 }}</ref> [[miR-155]], important in regulating alcohol-induced [[neuroinflammation]] responses, was found to be upregulated, suggesting the role of [[microglia]] and [[inflammatory cytokine]]s in alcohol pathophysiology.<ref name="Lippai">{{cite journal | vauthors = Lippai D, Bala S, Csak T, Kurt-Jones EA, Szabo G | title = Chronic alcohol-induced microRNA-155 contributes to neuroinflammation in a TLR4-dependent manner in mice | journal = PLOS ONE | volume = 8 | issue = 8 | pages = e70945 | year = 2013 | pmid = 23951048 | pmc = 3739772 | doi = 10.1371/journal.pone.0070945 | bibcode = 2013PLoSO...870945L | doi-access = free }}</ref> Downregulation of miR-382 was found in the [[nucleus accumbens]], a structure in the [[basal forebrain]] significant in regulating feelings of [[reward system|reward]] that power motivational habits. miR-382 is the target for the [[dopamine receptor D1]] (DRD1), and its overexpression results in the upregulation of DRD1 and delta [[fosB]], a transcription factor that activates a series of transcription events in the nucleus [[accumbens]] that ultimately result in addictive behaviors.<ref name="Li">{{cite journal | vauthors = Li J, Li J, Liu X, Qin S, Guan Y, Liu Y, Cheng Y, Chen X, Li W, Wang S, Xiong M, Kuzhikandathil EV, Ye JH, Zhang C | title = MicroRNA expression profile and functional analysis reveal that miR-382 is a critical novel gene of alcohol addiction | journal = EMBO Molecular Medicine | volume = 5 | issue = 9 | pages = 1402–14 | date = September 2013 | pmid = 23873704 | pmc = 3799494 | doi = 10.1002/emmm.201201900 }}</ref> Alternatively, overexpressing miR-382 resulted in attenuated drinking and the inhibition of [[Dopamine receptor D1|DRD1]] and delta [[fosB]] upregulation in rat models of alcoholism, demonstrating the possibility of using miRNA-targeted [[pharmaceutical drug|pharmaceuticals]] in treatments.<ref name="Li" />