Editing MicroRNA (section)

===Nervous system===
MiRNAs are crucial for the healthy development and function of the [[nervous system]].<ref>{{cite journal | vauthors = Cao DD, Li L, Chan WY | title = MicroRNAs: Key Regulators in the Central Nervous System and Their Implication in Neurological Diseases | journal = International Journal of Molecular Sciences | volume = 17 | issue = 6 | pages = 842 | date = May 2016 | pmid = 27240359 | pmc = 4926376 | doi = 10.3390/ijms17060842 | doi-access = free }}</ref> Previous studies demonstrate that miRNAs can regulate neuronal differentiation and maturation at various stages.<ref>{{cite journal | vauthors = Lang MF, Shi Y | title = Dynamic Roles of microRNAs in Neurogenesis | journal = Frontiers in Neuroscience | volume = 6 | pages = 71 | date = 2012 | pmid = 22661924 | pmc = 3356852 | doi = 10.3389/fnins.2012.00071 | doi-access = free }}</ref> MiRNAs also play important roles in [[Synaptogenesis|synaptic development]]<ref name="pmid19888283">{{cite journal | vauthors = Schratt G | title = microRNAs at the synapse | journal = Nature Reviews. Neuroscience | volume = 10 | issue = 12 | pages = 842–849 | date = December 2009 | pmid = 19888283 | doi = 10.1038/nrn2763 | s2cid = 3507952 }}</ref> (such as dendritogenesis or spine morphogenesis) and [[synaptic plasticity]]<ref>{{cite journal | vauthors = Luo M, Li L, Ding M, Niu Y, Xu X, Shi X, Shan N, Qiu Z, Piao F, Zhang C | title = Long-term potentiation and depression regulatory microRNAs were highlighted in Bisphenol A induced learning and memory impairment by microRNA sequencing and bioinformatics analysis | journal = PLOS ONE | volume = 18 | issue = 1 | pages = e0279029 | date = 2023-01-19 | pmid = 36656826 | pmc = 9851566 | doi = 10.1371/journal.pone.0279029 | doi-access = free | bibcode = 2023PLoSO..1879029L }}</ref> (contributing to learning and memory). Elimination of miRNA formation in mice by experimental silencing of [[Dicer]] has led to pathological outcomes, such as reduced neuronal size, motor abnormalities (when silenced in [[striatum|striatal]] neurons<ref>{{cite journal | vauthors = Cuellar TL, Davis TH, Nelson PT, Loeb GB, Harfe BD, Ullian E, McManus MT | title = Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 14 | pages = 5614–5619 | date = April 2008 | pmid = 18385371 | pmc = 2291142 | doi = 10.1073/pnas.0801689105 | doi-access = free | bibcode = 2008PNAS..105.5614C }}</ref>), and neurodegeneration (when silenced in [[forebrain]] neurons<ref>{{cite journal | vauthors = Hébert SS, Papadopoulou AS, Smith P, Galas MC, Planel E, Silahtaroglu AN, Sergeant N, Buée L, De Strooper B | title = Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration | journal = Human Molecular Genetics | volume = 19 | issue = 20 | pages = 3959–3969 | date = October 2010 | pmid = 20660113 | doi = 10.1093/hmg/ddq311 | doi-access = free }}</ref>). Altered miRNA expression has been found in neurodegenerative diseases (such as [[Alzheimer's disease]], [[Parkinson's disease]], and [[Huntington's disease]]<ref>{{cite journal | vauthors = Roy B, Lee E, Li T, Rampersaud M | title = Role of miRNAs in Neurodegeneration: From Disease Cause to Tools of Biomarker Discovery and Therapeutics | journal = Genes | volume = 13 | issue = 3 | pages = 425 | date = February 2022 | pmid = 35327979 | pmc = 8951370 | doi = 10.3390/genes13030425 | doi-access = free }}</ref>) as well as many psychiatric disorders (including [[epilepsy]],<ref>{{cite journal | vauthors = Henshall DC, Hamer HM, Pasterkamp RJ, Goldstein DB, Kjems J, Prehn JH, Schorge S, Lamottke K, Rosenow F | title = MicroRNAs in epilepsy: pathophysiology and clinical utility | journal = The Lancet. Neurology | volume = 15 | issue = 13 | pages = 1368–1376 | date = December 2016 | pmid = 27839653 | doi = 10.1016/S1474-4422(16)30246-0 | doi-access = free }}</ref> [[schizophrenia]], [[major depressive disorder|major depression]], [[bipolar disorder]], and [[anxiety disorder]]s<ref name="Hommers LG, Domschke K, Deckert J 2015 79-97">{{cite journal | vauthors = Hommers LG, Domschke K, Deckert J | title = Heterogeneity and individuality: microRNAs in mental disorders | journal = Journal of Neural Transmission | volume = 122 | issue = 1 | pages = 79–97 | date = January 2015 | pmid = 25395183 | doi = 10.1007/s00702-014-1338-4 | url = https://www.molekulartherapie.de/resources/Hommers_Heterogeneity+Individuality.pdf | url-status = live | s2cid-access = free | s2cid = 25088900 | archive-url = https://web.archive.org/web/20220523074509/https://molekulartherapie.de/resources/Hommers_Heterogeneity+Individuality.pdf | archive-date = May 23, 2022 }}</ref><ref name="pmid19568434">{{cite journal | vauthors = Feng J, Sun G, Yan J, Noltner K, Li W, Buzin CH, Longmate J, Heston LL, Rossi J, Sommer SS | title = Evidence for X-chromosomal schizophrenia associated with microRNA alterations | journal = PLOS ONE | volume = 4 | issue = 7 | pages = e6121 | date = July 2009 | pmid = 19568434 | pmc = 2699475 | doi = 10.1371/journal.pone.0006121 | veditors = Reif A | bibcode-access = free | doi-access = free | bibcode = 2009PLoSO...4.6121F }}</ref><ref name="pmid19721432">{{cite journal | vauthors = Beveridge NJ, Gardiner E, Carroll AP, Tooney PA, Cairns MJ | title = Schizophrenia is associated with an increase in cortical microRNA biogenesis | journal = Molecular Psychiatry | volume = 15 | issue = 12 | pages = 1176–1189 | date = December 2010 | pmid = 19721432 | pmc = 2990188 | doi = 10.1038/mp.2009.84 | doi-access = free }}</ref>).

====Stroke====
According to the Center for Disease Control and Prevention, Stroke is one of the leading causes of death and long-term disability in America. 87% of the cases are [[ischemic stroke]]s, which results from blockage in the artery of the brain that carries oxygen-rich blood. The obstruction of the blood flow means the brain cannot receive necessary nutrients, such as oxygen and glucose, and remove wastes, such as carbon dioxide.<ref>{{Cite web|url=https://www.cdc.gov/stroke/facts.htm|title=Stroke Facts |date=2019-03-15|website=Centers for Disease Control and Prevention |language=en-us|access-date=2019-12-05}}</ref><ref name=":0">{{cite journal | vauthors = Rink C, Khanna S | title = MicroRNA in ischemic stroke etiology and pathology | journal = Physiological Genomics | volume = 43 | issue = 10 | pages = 521–528 | date = May 2011 | pmid = 20841499 | pmc = 3110894 | doi = 10.1152/physiolgenomics.00158.2010 }}</ref> miRNAs plays a role in posttranslational gene silencing by targeting genes in the pathogenesis of cerebral ischemia, such as the inflammatory, angiogenesis, and apoptotic pathway.<ref>{{cite journal | vauthors = Ouyang YB, Stary CM, Yang GY, Giffard R | title = microRNAs: innovative targets for cerebral ischemia and stroke | journal = Current Drug Targets | volume = 14 | issue = 1 | pages = 90–101 | date = January 2013 | pmid = 23170800 | pmc = 3673881 | doi = 10.2174/138945013804806424 }}</ref>&nbsp;

====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" />