Login Register Cart 0
Generic placeholder image

Central Nervous System Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5249
ISSN (Online): 1875-6166

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

The Computational Analysis Conducted on miRNA Target Sites in Association with SNPs at 3’UTR of ADHD-implicated Genes

Author(s): Adel Abdi, Mina Zafarpiran and Zeinab S. Farsani*

Volume 20, Issue 1, 2020

Page: [58 - 75] Pages: 18

DOI: 10.2174/1871524919666191014104843

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) is a frequent chronic neuropsychiatric disorder in which different factors including environmental, genetic, and epigenetic factors play an important role in its pathogenesis. One of the effective epigenetic factors is recognized as MicroRNAs (miRNAs). On the other hand, it has been indicated that the single nucleotide polymorphism (SNPs) present within 3'UTR (3' untranslated region) of mRNAs can influence the regulation of miRNA-mediated gene and susceptibility to a diversity of human diseases.

Methods: The purpose of this study was to analyze the SNPs within the 3'UTR of miRNA target genes associated with ADHD. 3'UTR genetic variants were identified in all genes associated with ADHD using DisGeNET, dbGaP, Ovid, DAVID, Web of knowledge, and SNPs databases. miRNA's target prediction databases were applied in order to predict the miRNA binding sites. 124 SNPs with MAF>0.05 were identified located in the binding site of the miRNA of 35 genes amongst 51 genes associated with ADHD.

Results: Bioinformatics analysis predicted 81 MRE (miRNA recognition elements)-creating SNPs, 101 MRE-breaking SNPs, 61 MRE-enhancing SNPs, and finally predicted 41 MREdecreasing SNPs in the 3'UTR of ADHD-implicated genes. These candidate SNPs within these genes miRNA binding sites can alter the miRNAs binding, and consequently, lead to mRNA gene regulation.

Conclusion: Therefore, these miRNA and MRE-SNPs may play important roles in ADHD, and because of that, they would be valuable for further investigation in the field of functional verification.

Keywords: ADHA, SNP, miRNA, miRNA binding sites, ADHD- related genes, miRNA target genes.

« Previous
Graphical Abstract

[1]
Faraone, S.V.; Asherson, P.; Banaschewski, T.; Biederman, J.; Buitelaar, J.K.; Ramos-Quiroga, J.A.; Rohde, L.A.; Sonuga-Barke, E.J.; Tannock, R.; Franke, B. Attention-deficit/hyperactivity disorder. Nat. Rev. Dis. Primers, 2015, 1, 15020.
[http://dx.doi.org/10.1038/nrdp.2015.20] [PMID: 27189265]
[2]
Vahia, V.N. Diagnostic and statistical manual of mental disorders 5: A quick glance. Indian J. Psychiatry, 2013, 55(3), 220-223.
[http://dx.doi.org/10.4103/0019-5545.117131] [PMID: 24082241]
[3]
(a) Polanczyk, G.; de Lima, M.S.; Horta, B.L.; Biederman, J.; Rohde, L.A. The worldwide prevalence of ADHD: A systematic review and metaregression analysis. Am. J. Psychiatry, 2007, 164(6), 942-948.
[http://dx.doi.org/10.1176/ajp.2007.164.6.942] [PMID: 17541055]
(b) Simon, V.; Czobor, P.; Bálint, S.; Mészáros, A.; Bitter, I. Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis. Br. J. Psychiatry, 2009, 194(3), 204-211.
[http://dx.doi.org/10.1192/bjp.bp.107.048827] [PMID: 19252145]
[4]
(a) Mill, J.; Petronis, A. Pre- and peri-natal environmental risks for attention-deficit hyperactivity disorder (ADHD): The potential role of epigenetic processes in mediating susceptibility. J. Child Psychol. Psychiatry, 2008, 49(10), 1020-1030.
[http://dx.doi.org/10.1111/j.1469-7610.2008.01909.x] [PMID: 18492038]
(b) Schuch, V.; Utsumi, D.A.; Costa, T.V.; Kulikowski, L.D.; Muszkat, M. Attention deficit hyperactivity disorder in the light of the epigenetic paradigm. Front. Psychiatry, 2015, 6, 126.
[http://dx.doi.org/10.3389/fpsyt.2015.00126] [PMID: 26441687]
[5]
(a) Xu, B.; Hsu, P.K.; Karayiorgou, M.; Gogos, J.A. MicroRNA dysregulation in neuropsychiatric disorders and cognitive dysfunction. Neurobiol. Dis., 2012, 46(2), 291-301.
[http://dx.doi.org/10.1016/j.nbd.2012.02.016] [PMID: 22406400]
(b) Smalheiser, N.R.; Lugli, G.; Zhang, H.; Rizavi, H.; Cook, E.H.; Dwivedi, Y. Expression of microRNAs and other small RNAs in prefrontal cortex in schizophrenia, bipolar disorder and depressed subjects. PLoS One, 2014, 9(1)e86469
[http://dx.doi.org/10.1371/journal.pone.0086469] [PMID: 24475125]
(c) Abu-Elneel, K.; Liu, T.; Gazzaniga, F.S.; Nishimura, Y.; Wall, D.P.; Geschwind, D.H.; Lao, K.; Kosik, K.S. Heterogeneous dysregulation of microRNAs across the autism spectrum. Neurogenetics, 2008, 9(3), 153-161.
[http://dx.doi.org/10.1007/s10048-008-0133-5] [PMID: 18563458]
(d) Mellios, N.; Sur, M. The emerging role of microRNAs in schizophrenia and autism spectrum disorders. Front. Psychiatry, 2012, 3, 39.
[http://dx.doi.org/10.3389/fpsyt.2012.00039] [PMID: 22539927]
(e) Wang, L-J.; Li, S-C.; Lee, M-J.; Chou, M-C.; Chou, W-J.; Lee, S-Y.; Hsu, C-W.; Huang, L-H.; Kuo, H-C. Blood-bourne microRNA biomarker evaluation in attention-deficit/hyperactivity disorder of han chinese individuals: An exploratory study. Front. Psychiatry, 2018, 9, 227.
[http://dx.doi.org/10.3389/fpsyt.2018.00227] [PMID: 29896131]
[6]
(a) Kosik, K.S. The neuronal microRNA system. Nat. Rev. Neurosci., 2006, 7(12), 911-920.
[http://dx.doi.org/10.1038/nrn2037] [PMID: 17115073]
(b) Ye, Y.; Xu, H.; Su, X.; He, X. Role of microRNA in governing synaptic plasticity. Neural Plast., 2016, 2016 4959523
[http://dx.doi.org/10.1155/2016/4959523] [PMID: 27034846]
[7]
Saunders, M.A.; Liang, H.; Li, W-H. Human polymorphism at microRNAs and microRNA target sites. Proc. Natl. Acad. Sci. USA, 2007, 104(9), 3300-3305.
[http://dx.doi.org/10.1073/pnas.0611347104] [PMID: 17360642]
[8]
(a) Ryan, B.M.; Robles, A.I.; Harris, C.C. Genetic variation in microRNA networks: The implications for cancer research. Nat. Rev. Cancer, 2010, 10(6), 389-402.
[http://dx.doi.org/10.1038/nrc2867] [PMID: 20495573]
(b) Kang, B.W.; Jeon, H.S.; Chae, Y.S.; Lee, S.J.; Park, J.S.; Choi, G.S.; Kim, J.G. Impact of genetic variation in microRNA-binding site on susceptibility to colorectal cancer. Anticancer Res., 2016, 36(7), 3353-3361. [https://www.ncbi.nlm.nih.gov/pubmed/27354594
[PMID: 27354594]
[9]
(a) Sethupathy, P.; Collins, F.S. MicroRNA target site polymorphisms and human disease. Trends Genet., 2008, 24(10), 489-497.
[http://dx.doi.org/10.1016/j.tig.2008.07.004] [PMID: 18778868]
(b) Moszyńska, A.; Gebert, M.; Collawn, J.F.; Bartoszewski, R. SNPs in microRNA target sites and their potential role in human disease. Open Biol., 2017, 7(4) 170019
[http://dx.doi.org/10.1098/rsob.170019] [PMID: 28381629]
[10]
(a) Wang, G.; van der Walt, J.M.; Mayhew, G.; Li, Y.J.; Züchner, S.; Scott, W.K.; Martin, E.R.; Vance, J.M. Variation in the miRNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of alpha-synuclein. Am. J. Hum. Genet., 2008, 82(2), 283-289.
[http://dx.doi.org/10.1016/j.ajhg.2007.09.021] [PMID: 18252210]
(b) Ghanbari, M.; Ikram, M.A.; de Looper, H.W.J.; Hofman, A.; Erkeland, S.J.; Franco, O.H.; Dehghan, A. Genome-wide identification of microRNA-related variants associated with risk of Alzheimer’s disease. Sci. Rep., 2016, 6, 28387.
[http://dx.doi.org/10.1038/srep28387] [PMID: 27328823]
[11]
Georges, M.; Coppieters, W.; Charlier, C. Polymorphic miRNA-mediated gene regulation: Contribution to phenotypic variation and disease. Curr. Opin. Genet. Dev., 2007, 17(3), 166-176.
[http://dx.doi.org/10.1016/j.gde.2007.04.005] [PMID: 17467975]
[12]
Zhang, L.; Chang, S.; Li, Z.; Zhang, K.; Du, Y.; Ott, J.; Wang, J. ADHDgene: A genetic database for attention deficit hyperactivity disorder. Nucleic Acids Res., 2012, 40(Database issue), D1003-D1009.
[http://dx.doi.org/10.1093/nar/gkr992] [PMID: 22080511]
[13]
Piñero, J.; Bravo, À.; Queralt-Rosinach, N.; Gutiérrez-Sacristán, A.; Deu-Pons, J.; Centeno, E.; García-García, J.; Sanz, F.; Furlong, L.I. DisGeNET: A comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res., 2017, 45(D1), D833-D839.
[http://dx.doi.org/10.1093/nar/gkw943] [PMID: 27924018]
[14]
Bruno, A.E.; Li, L.; Kalabus, J.L.; Pan, Y.; Yu, A.; Hu, Z. miRdSNP: A database of disease-associated SNPs and microRNA target sites on 3'UTRs of human genes. BMC Genomics, 2012, 13(1), 44.
[http://dx.doi.org/10.1186/1471-2164-13-44] [PMID: 22276777]
[15]
Liu, C.; Zhang, F.; Li, T.; Lu, M.; Wang, L.; Yue, W.; Zhang, D. MirSNP, a database of polymorphisms altering miRNA target sites, identifies miRNA-related SNPs in GWAS SNPs and eQTLs. BMC Genomics, 2012, 13(1), 661.
[http://dx.doi.org/10.1186/1471-2164-13-661] [PMID: 23173617]
[16]
Kumar, A.; Wong, A.K-L.; Tizard, M.L.; Moore, R.J.; Lefèvre, C. miRNA_Targets: A database for miRNA target predictions in coding and non-coding regions of mRNAs. Genomics, 2012, 100(6), 352-356.
[http://dx.doi.org/10.1016/j.ygeno.2012.08.006] [PMID: 22940442]
[17]
Lipchina, I.; Elkabetz, Y.; Hafner, M.; Sheridan, R.; Mihailovic, A.; Tuschl, T.; Sander, C.; Studer, L.; Betel, D. Genome-wide identification of microRNA targets in human ES cells reveals a role for miR-302 in modulating BMP response. Genes Dev., 2011, 25(20), 2173-2186.
[http://dx.doi.org/10.1101/gad.17221311] [PMID: 22012620]
[18]
Ziebarth, J.D.; Bhattacharya, A.; Chen, A.; Cui, Y. PolymiRTS Database 2.0: linking polymorphisms in microRNA target sites with human diseases and complex traits. Nucleic Acids Res., 2012, 40(Database issue), D216-D221.
[http://dx.doi.org/10.1093/nar/gkr1026] [PMID: 22080514]
[19]
Landi, D.; Barale, R.; Gemignani, F.; Landi, S. Prediction of the biological effect of polymorphisms within microRNA binding sites.In: MicroRNA and Cancer; Humana Press: Totowa, NJ, 2011, pp. 197-210.
[http://dx.doi.org/10.1007/978-1-60761-863-8_14]
[20]
Faraone, S.V.; Perlis, R.H.; Doyle, A.E.; Smoller, J.W.; Goralnick, J.J.; Holmgren, M.A.; Sklar, P. Molecular genetics of attention-deficit/hyperactivity disorder. Biol. Psychiatry, 2005, 57(11), 1313-1323.
[http://dx.doi.org/10.1016/j.biopsych.2004.11.024] [PMID: 15950004]
[21]
Shastry, B.S. SNPs: Impact on gene function and phenotype. Methods Mol. Biol., 2009, 578, 3-22.
[http://dx.doi.org/10.1007/978-1-60327-411-1_1] [PMID: 19768584]
[22]
Huang, H-C.; Wu, L.S-H.; Yu, S-C.; Wu, B-J.; Lua, A.C.; Lee, S-M.; Liu, C-Z. The alpha-2A adrenergic receptor gene-1291C/G single nucleotide polymorphism is associated with the efficacy of methylphenidate in treating taiwanese children and adolescents with attention-deficit hyperactivity disorder. Psychiatry Investig., 2018, 15(3), 306-312.
[http://dx.doi.org/10.30773/pi.2017.07.24] [PMID: 29486545]
[23]
Lario, S.; Calls, J.; Cases, A.; Oriola, J.; Torras, A.; Rivera, F. MspI identifies a biallelic polymorphism in the promoter region of the alpha 2A-adrenergic receptor gene. Clin. Genet., 1997, 51(2), 129-130.
[http://dx.doi.org/10.1111/j.1399-0004.1997.tb02436.x] [PMID: 9112004]
[24]
Alamo, C.; López-Muñoz, F.; Sánchez-García, J. Mechanism of action of guanfacine: A postsynaptic differential approach to the treatment of attention deficit hyperactivity disorder (adhd). Actas Esp. Psiquiatr., 2016, 44(3), 107-112. [https://www.ncbi.nlm.nih.gov/pubmed/27254403
[PMID: 27254403]
[25]
Stahl, S.M. Mechanism of action of alpha 2A-adrenergic agonists in attention-deficit/hyperactivity disorder with or without oppositional symptoms. J. Clin. Psychiatry, 2010, 71(3), 223-224.
[http://dx.doi.org/10.4088/JCP.09bs05899pur] [PMID: 20331927]
[26]
(a) Kertesz, M.; Iovino, N.; Unnerstall, U.; Gaul, U.; Segal, E. The role of site accessibility in microRNA target recognition. Nat. Genet., 2007, 39(10), 1278-1284.
[http://dx.doi.org/10.1038/ng2135] [PMID: 17893677]
(b) Wang, G.; van der Walt, J.M.; Mayhew, G.; Li, Y-J.; Züchner, S.; Scott, W.K.; Martin, E.R.; Vance, J.M. Variation in the miRNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of α-synuclein. Am. J. Hum. Genet., 2008, 82(2), 283-289.
[http://dx.doi.org/10.1016/j.ajhg.2007.09.021] [PMID: 18252210]
[27]
Garcia-Martínez, I.; Sánchez-Mora, C.; Pagerols, M.; Richarte, V.; Corrales, M.; Fadeuilhe, C.; Cormand, B.; Casas, M.; Ramos-Quiroga, J.A.; Ribasés, M. Preliminary evidence for association of genetic variants in pri-miR-34b/c and abnormal miR-34c expression with attention deficit and hyperactivity disorder. Transl. Psychiatry, 2016, 6(8)e879
[http://dx.doi.org/10.1038/tp.2016.151] [PMID: 27576168]
[28]
Wu, L.H.; Peng, M.; Yu, M.; Zhao, Q.L.; Li, C.; Jin, Y.T.; Jiang, Y.; Chen, Z.Y.; Deng, N.H.; Sun, H.; Wu, X.Z. Circulating microRNA Let-7d in attention-deficit/hyperactivity disorder. Neuromolecular Med., 2015, 17(2), 137-146.
[http://dx.doi.org/10.1007/s12017-015-8345-y] [PMID: 25724585]
[29]
Srivastav, S.; Walitza, S.; Grünblatt, E. Emerging role of miRNA in attention deficit hyperactivity disorder: A systematic review. Atten. Defic. Hyperact. Disord., 2018, 10(1), 49-63.
[http://dx.doi.org/10.1007/s12402-017-0232-y] [PMID: 28493018]
[30]
Kandemir, H.; Erdal, M.E.; Selek, S.; Ay, O.I.; Karababa, I.F.; Kandemir, S.B.; Ay, M.E.; Yılmaz, S.G.; Bayazıt, H.; Taşdelen, B. Evaluation of several micro RNA (miRNA) levels in children and adolescents with attention deficit hyperactivity disorder. Neurosci. Lett., 2014, 580, 158-162.
[http://dx.doi.org/10.1016/j.neulet.2014.07.060] [PMID: 25123444]
[31]
Papagregoriou, G.; Erguler, K.; Dweep, H.; Voskarides, K.; Koupepidou, P.; Athanasiou, Y.; Pierides, A.; Gretz, N.; Felekkis, K.N.; Deltas, C. A miR-1207-5p binding site polymorphism abolishes regulation of HBEGF and is associated with disease severity in CFHR5 nephropathy. PLoS One, 2012, 7(2)e31021
[http://dx.doi.org/10.1371/journal.pone.0031021] [PMID: 22319602]
[32]
He, Y.; Yu, D.; Zhu, L.; Zhong, S.; Zhao, J.; Tang, J. miR-149 in human cancer: A systemic review. J. Cancer, 2018, 9(2), 375-388.
[http://dx.doi.org/10.7150/jca.21044] [PMID: 29344284]
[33]
Gallelli, L.; Cione, E.; Peltrone, F.; Siviglia, S.; Verano, A.; Chirchiglia, D.; Zampogna, S.; Guidetti, V.; Sammartino, L.; Montana, A.; Caroleo, M.C.; De Sarro, G.; Di Mizio, G. Hsa-miR-34a-5p and hsa-miR-375 as biomarkers for monitoring the effects of drug treatment for migraine pain in children and adolescents: A pilot study. J. Clin. Med., 2019, 8(7)E928
[http://dx.doi.org/10.3390/jcm8070928] [PMID: 31252698]
[34]
Kim, A.H.; Reimers, M.; Maher, B.; Williamson, V.; McMichael, O.; McClay, J.L.; van den Oord, E.J.C.G.; Riley, B.P.; Kendler, K.S.; Vladimirov, V.I. MicroRNA expression profiling in the prefrontal cortex of individuals affected with schizophrenia and bipolar disorders. Schizophr. Res., 2010, 124(1-3), 183-191.
[http://dx.doi.org/10.1016/j.schres.2010.07.002] [PMID: 20675101]
[35]
Hommers, L.G.; Domschke, K.; Deckert, J. Heterogeneity and individuality: microRNAs in mental disorders. J. Neural Trans., 2015, 122(1), 79-97.
[36]
Li, W.; Liu, M.; Feng, Y.; Xu, Y.F.; Huang, Y.F.; Che, J.P.; Wang, G.C.; Yao, X.D.; Zheng, J.H. Downregulated miR-646 in clear cell renal carcinoma correlated with tumour metastasis by targeting the nin one binding protein (NOB1). Br. J. Cancer, 2014, 111(6), 1188-1200.
[http://dx.doi.org/10.1038/bjc.2014.382] [PMID: 25010867]
[37]
Bian, Y.; Guo, J.; Qiao, L.; Sun, X. miR-3189-3p mimics enhance the effects of S100A4 siRNA on the inhibition of proliferation and migration of gastric cancer cells by targeting CFL2. Int. J. Mol. Sci., 2018, 19(1), 236.
[http://dx.doi.org/10.3390/ijms19010236] [PMID: 29342841]
[38]
Collares, C.V.A.; Evangelista, A.F.; Xavier, D.J.; Rassi, D.M.; Arns, T.; Foss-Freitas, M.C.; Foss, M.C.; Puthier, D.; Sakamoto-Hojo, E.T.; Passos, G.A.; Donadi, E.A. Identifying common and specific microRNAs expressed in peripheral blood mononuclear cell of type 1, type 2, and gestational diabetes mellitus patients. BMC Res. Notes, 2013, 6, 491.
[http://dx.doi.org/10.1186/1756-0500-6-491] [PMID: 24279768]
[39]
Cheng, D.; Li, J.; Zhang, L.; Hu, L. miR-142-5p suppresses proliferation and promotes apoptosis of human osteosarcoma cell line, HOS, by targeting PLA2G16 through the ERK1/2 signaling pathway. Oncol. Lett., 2019, 17(1), 1363-1371.
[PMID: 30655907]
[40]
Wang, Q.; Wang, Y.; Ji, W.; Zhou, G.; He, K.; Li, Z.; Chen, J.; Li, W.; Wen, Z.; Shen, J.; Qiang, Y.; Ji, J.; Wang, Y.; Shi, Y.; Yi, Q.; Wang, Y. SNAP25 is associated with schizophrenia and major depressive disorder in the Han Chinese population. J. Clin. Psychiatry, 2015, 76(1), e76-e82.
[http://dx.doi.org/10.4088/JCP.13m08962] [PMID: 25650683]
[41]
He, Z.; Yi, J.; Liu, X.; Chen, J.; Han, S.; Jin, L.; Chen, L.; Song, H. MiR-143-3p functions as a tumor suppressor by regulating cell proliferation, invasion and epithelial-mesenchymal transition by targeting QKI-5 in esophageal squamous cell carcinoma. Mol. Cancer, 2016, 15(1), 51.
[http://dx.doi.org/10.1186/s12943-016-0533-3] [PMID: 27358073]
[42]
Satoh, J. Molecular network analysis of human microRNA targetome: from cancers to Alzheimer’s disease. BioData Min., 2012, 5(1), 17.
[http://dx.doi.org/10.1186/1756-0381-5-17] [PMID: 23034144]

Rights & Permissions Print Cite
Article Metrics
4
© 2024 Bentham Science Publishers | Privacy Policy