Next-generation sequencing profiling of miRNAs in individuals with 22q11.2 deletion syndrome revealed altered expression of miR-185-5p.
22q11.2 deletion syndrome
Next-generation sequencing
miR-185-5p
miRNA
Journal
Human genomics
ISSN: 1479-7364
Titre abrégé: Hum Genomics
Pays: England
ID NLM: 101202210
Informations de publication
Date de publication:
13 Jun 2024
13 Jun 2024
Historique:
received:
16
10
2023
accepted:
25
05
2024
medline:
14
6
2024
pubmed:
14
6
2024
entrez:
13
6
2024
Statut:
epublish
Résumé
The 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with highly variable phenotypic manifestations, even though most patients present the typical 3 Mb microdeletion, usually affecting the same ~ 106 genes. One of the genes affected by this deletion is DGCR8, which plays a crucial role in miRNA biogenesis. Therefore, the haploinsufficiency of DGCR8 due to this microdeletion can alter the modulation of the expression of several miRNAs involved in a range of biological processes. In this study, we used next-generation sequencing to evaluate the miRNAs profiles in the peripheral blood of 12 individuals with typical 22q11DS compared to 12 healthy matched controls. We used the DESeq2 package for differential gene expression analysis and the DIANA-miTED dataset to verify the expression of differentially expressed miRNAs in other tissues. We used miRWalk to predict the target genes of differentially expressed miRNAs. Here, we described two differentially expressed miRNAs in patients compared to controls: hsa-miR-1304-3p, located outside the 22q11.2 region, upregulated in patients, and hsa-miR-185-5p, located in the 22q11.2 region, which showed downregulation. Expression of miR-185-5p is observed in tissues frequently affected in patients with 22q11DS, and previous studies have reported its downregulation in individuals with 22q11DS. hsa-miR-1304-3p has low expression in blood and, thus, needs more validation, though using a sensitive technology allowed us to identify differences in expression between patients and controls. Thus, lower expression of miR-185-5p can be related to the 22q11.2 deletion and DGCR8 haploinsufficiency, leading to phenotypic consequences in 22q11.2DS patients, while higher expression of hsa-miR-1304-3p might be related to individual genomic variances due to the heterogeneous background of the Brazilian population.
Sections du résumé
BACKGROUND
BACKGROUND
The 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with highly variable phenotypic manifestations, even though most patients present the typical 3 Mb microdeletion, usually affecting the same ~ 106 genes. One of the genes affected by this deletion is DGCR8, which plays a crucial role in miRNA biogenesis. Therefore, the haploinsufficiency of DGCR8 due to this microdeletion can alter the modulation of the expression of several miRNAs involved in a range of biological processes.
RESULTS
RESULTS
In this study, we used next-generation sequencing to evaluate the miRNAs profiles in the peripheral blood of 12 individuals with typical 22q11DS compared to 12 healthy matched controls. We used the DESeq2 package for differential gene expression analysis and the DIANA-miTED dataset to verify the expression of differentially expressed miRNAs in other tissues. We used miRWalk to predict the target genes of differentially expressed miRNAs. Here, we described two differentially expressed miRNAs in patients compared to controls: hsa-miR-1304-3p, located outside the 22q11.2 region, upregulated in patients, and hsa-miR-185-5p, located in the 22q11.2 region, which showed downregulation. Expression of miR-185-5p is observed in tissues frequently affected in patients with 22q11DS, and previous studies have reported its downregulation in individuals with 22q11DS. hsa-miR-1304-3p has low expression in blood and, thus, needs more validation, though using a sensitive technology allowed us to identify differences in expression between patients and controls.
CONCLUSIONS
CONCLUSIONS
Thus, lower expression of miR-185-5p can be related to the 22q11.2 deletion and DGCR8 haploinsufficiency, leading to phenotypic consequences in 22q11.2DS patients, while higher expression of hsa-miR-1304-3p might be related to individual genomic variances due to the heterogeneous background of the Brazilian population.
Identifiants
pubmed: 38872198
doi: 10.1186/s40246-024-00625-5
pii: 10.1186/s40246-024-00625-5
doi:
Substances chimiques
MicroRNAs
0
MIRN185 microRNA, human
0
DGCR8 protein, human
0
RNA-Binding Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
64Subventions
Organisme : Fundação de Amparo à Pesquisa do Estado de São Paulo
ID : #2019/21644-0
Informations de copyright
© 2024. The Author(s).
Références
McDonald-McGinn DM, Sullivan KE, Marino B, Philip N, Swillen A, Vorstman JAS, et al. 22q11.2 deletion syndrome. Nat Rev Dis Primers. 2015;1(1):15071.
pubmed: 27189754
pmcid: 4900471
doi: 10.1038/nrdp.2015.71
Grati FR, Molina Gomes D, Ferreira JCPB, Dupont C, Alesi V, Gouas L, et al. Prevalence of recurrent pathogenic microdeletions and microduplications in over 9500 pregnancies. Prenat Diagn. 2015;35(8):801–9.
pubmed: 25962607
doi: 10.1002/pd.4613
Shaikh TH, Kurahashi H, Saitta SC, O’Hare AM, Hu P, Roe BA, et al. Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis. Hum Mol Genet. 2000;9(4):489–501.
pubmed: 10699172
doi: 10.1093/hmg/9.4.489
Edelmann L, Pandita RK, Morrow BE. Low-Copy repeats mediate the common 3-Mb deletion in patients with Velo-cardio-facial syndrome. Am J Hum Genet. 1999;64(4):1076–86.
pubmed: 10090893
pmcid: 1377832
doi: 10.1086/302343
Karbarz M. Consequences of 22q11.2 Microdeletion on the genome, Individual and Population levels. Genes (Basel). 2020;11(9):977.
pubmed: 32842603
doi: 10.3390/genes11090977
Robin NH, Shprintzen RJ. Defining the clinical spectrum of deletion 22q11.2. J Pediatr. 2005;147(1):90–6.
pubmed: 16027702
doi: 10.1016/j.jpeds.2005.03.007
Du Q, de la Morena MT, van Oers NSC. The Genetics and epigenetics of 22q11.2 deletion syndrome. Front Genet. 2020;10.
Racedo SE, Liu Y, Shi L, Zheng D, Morrow BE. Dgcr8 functions in the secondary heart field for outflow tract and right ventricle development in mammals. Dev Biol. 2023.
Leitão AL, Enguita FJ. A structural view of miRNA Biogenesis and function. Noncoding RNA. 2022;8(1):10.
pubmed: 35202084
pmcid: 8874510
Kozomara A, Birgaoanu M, Griffiths-Jones S. miRBase: from microRNA sequences to function. Nucleic Acids Res. 2019;47(D1):D155–62.
pubmed: 30423142
doi: 10.1093/nar/gky1141
Bartel DP, MicroRNAs. Cell. 2004;116(2):281–97.
pubmed: 14744438
doi: 10.1016/S0092-8674(04)00045-5
Brzustowicz LM, Bassett AS. miRNA-mediated risk for schizophrenia in 22q11.2 deletion syndrome. Front Genet. 2012;3(DEC).
Sellier C, Hwang VJ, Dandekar R, Durbin-Johnson B, Charlet-Berguerand N, Ander BP, et al. Decreased DGCR8 expression and miRNA dysregulation in individuals with 22q11.2 deletion syndrome. PLoS ONE. 2014;9(8):e103884.
pubmed: 25084529
pmcid: 4118991
doi: 10.1371/journal.pone.0103884
de la Morena MT, Eitson JL, Dozmorov IM, Belkaya S, Hoover AR, Anguiano E, et al. Signature MicroRNA expression patterns identified in humans with 22q11.2 deletion/DiGeorge syndrome. Clin Immunol. 2013;147(1):11–22.
pubmed: 23454892
pmcid: 3748608
doi: 10.1016/j.clim.2013.01.011
Koshiol J, Wang E, Zhao Y, Marincola F, Landi MT. Strengths and limitations of Laboratory procedures for MicroRNA Detection. Cancer Epidemiol Biomarkers Prev. 2010;19(4):907–11.
pubmed: 20332265
pmcid: 2852469
doi: 10.1158/1055-9965.EPI-10-0071
Ibberson D, Benes V, Muckenthaler MU, Castoldi M. RNA degradation compromises the reliability of microRNA expression profiling. BMC Biotechnol. 2009;9(1):102.
pubmed: 20025722
pmcid: 2805631
doi: 10.1186/1472-6750-9-102
Patil AH, Halushka MK. miRge3.0: a comprehensive microRNA and tRF sequencing analysis pipeline. NAR Genom Bioinform. 2021;3(3).
Love MI, Huber W, Anders S. Moderated estimation of Fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550.
pubmed: 25516281
pmcid: 4302049
doi: 10.1186/s13059-014-0550-8
Potla P, Ali SA, Kapoor M. A bioinformatics approach to microRNA-sequencing analysis. Osteoarthr Cartil Open. 2021;3(1):100131.
pubmed: 36475076
doi: 10.1016/j.ocarto.2020.100131
Kavakiotis I, Alexiou A, Tastsoglou S, Vlachos IS, Hatzigeorgiou AG. DIANA-miTED: a microRNA tissue expression database. Nucleic Acids Res. 2022;50(D1):D1055–61.
pubmed: 34469540
doi: 10.1093/nar/gkab733
Sticht C, De La Torre C, Parveen A, Gretz N. miRWalk: an online resource for prediction of microRNA binding sites. PLoS ONE. 2018;13(10):e0206239.
pubmed: 30335862
pmcid: 6193719
doi: 10.1371/journal.pone.0206239
Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016;44(W1):W90–7.
pubmed: 27141961
pmcid: 4987924
doi: 10.1093/nar/gkw377
Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, Meirelles GV, et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics. 2013;14(1):128.
pubmed: 23586463
pmcid: 3637064
doi: 10.1186/1471-2105-14-128
Xie Z, Bailey A, Kuleshov MV, Clarke DJB, Evangelista JE, Jenkins SL et al. Gene Set Knowledge Discovery with Enrichr. Curr Protoc. 2021;1(3).
Dantas AG, Santoro ML, Nunes N, de Mello CB, Pimenta LSE, Meloni VA, et al. Downregulation of genes outside the deleted region in individuals with 22q11.2 deletion syndrome. Hum Genet. 2019;138(1):93–103.
pubmed: 30627818
doi: 10.1007/s00439-018-01967-6
Stark KL, Xu B, Bagchi A, Lai WS, Liu H, Hsu R, et al. Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model. Nat Genet. 2008;40(6):751–60.
pubmed: 18469815
doi: 10.1038/ng.138
Earls LR, Fricke RG, Yu J, Berry RB, Baldwin LT, Zakharenko SS. Age-dependent MicroRNA control of synaptic plasticity in 22q11 deletion syndrome and Schizophrenia. J Neurosci. 2012;32(41):14132–44.
pubmed: 23055483
pmcid: 3486522
doi: 10.1523/JNEUROSCI.1312-12.2012
Chun S, Du F, Westmoreland JJ, Han SB, Wang YD, Eddins D, et al. Thalamic mir-338-3p mediates auditory thalamocortical disruption and its late onset in models of 22q11.2 microdeletion. Nat Med. 2017;23(1):39–48.
pubmed: 27892953
doi: 10.1038/nm.4240
Zhao D, Lin M, Chen J, Pedrosa E, Hrabovsky A, Fourcade HM, et al. MicroRNA profiling of neurons generated using Induced pluripotent stem cells derived from patients with Schizophrenia and Schizoaffective Disorder, and 22q11.2 Del. PLoS ONE. 2015;10(7):e0132387.
pubmed: 26173148
pmcid: 4501820
doi: 10.1371/journal.pone.0132387
Toyoshima M, Akamatsu W, Okada Y, Ohnishi T, Balan S, Hisano Y, et al. Analysis of induced pluripotent stem cells carrying 22q11.2 deletion. Transl Psychiatry. 2016;6(11):e934–934.
pubmed: 27801899
pmcid: 5314118
doi: 10.1038/tp.2016.206
Ying S, Heung T, Zhang Z, Yuen RKC, Bassett AS. Schizophrenia Risk mediated by microRNA target genes overlapped by genome-wide Rare Copy Number Variation in 22q11.2 deletion syndrome. Front Genet. 2022;13.
Kim JO, Song DW, Kwon EJ, Hong SE, Song HK, Min CK, et al. miR-185 plays an anti-hypertrophic role in the heart via multiple targets in the calcium-signaling pathways. PLoS ONE. 2015;10(3):e0122509.
pubmed: 25767890
pmcid: 4358957
doi: 10.1371/journal.pone.0122509
Poirsier C, Besseau-Ayasse J, Schluth-Bolard C, Toutain J, Missirian C, Le Caignec C, et al. A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH. Eur J Hum Genet. 2016;24(6):844–51.
pubmed: 26508576
doi: 10.1038/ejhg.2015.219
Cancrini C, Puliafito P, Digilio MC, Soresina A, Martino S, Rondelli R, et al. Clinical features and Follow-Up in patients with 22q11.2 deletion syndrome. J Pediatr. 2014;164(6):1475–e14802.
pubmed: 24657119
doi: 10.1016/j.jpeds.2014.01.056
Campbell IM, Sheppard SE, Crowley TB, McGinn DE, Bailey A, McGinn MJ, et al. What is new with 22q? An update from the 22q and you center at the children’s hospital of Philadelphia. Am J Med Genet A. 2018;176(10):2058–69.
pubmed: 30380191
pmcid: 6501214
doi: 10.1002/ajmg.a.40637
Sabaie H, Gharesouran J, Asadi MR, Farhang S, Ahangar NK, Brand S, et al. Downregulation of miR-185 is a common pathogenic event in 22q11.2 deletion syndrome-related and idiopathic schizophrenia. Metab Brain Dis. 2022;37(4):1175–84.
pubmed: 35075501
doi: 10.1007/s11011-022-00918-5
Forstner AJ, Basmanav FB, Mattheisen M, Böhmer AC, Hollegaard MV, Janson E, et al. Investigation of the involvement of MIR185 and its target genes in the development of schizophrenia. J Psychiatry Neurosci. 2014;39(6):386–96.
pubmed: 24936775
pmcid: 4214873
doi: 10.1503/jpn.130189
Benetti S, Mechelli A, Picchioni M, Broome M, Williams S, McGuire P. Functional integration between the posterior hippocampus and prefrontal cortex is impaired in both first episode schizophrenia and the at risk mental state. Brain. 2009;132(9):2426–36.
pubmed: 19420091
doi: 10.1093/brain/awp098
Karayiorgou M, Simon TJ, Gogos JA. 22q11.2 microdeletions: linking DNA structural variation to brain dysfunction and schizophrenia. Nat Rev Neurosci. 2010;11(6):402–16.
pubmed: 20485365
pmcid: 2977984
doi: 10.1038/nrn2841
Nicoletti A, S de, Visacri MB, Ronda da, SC da CR, do PE V, Quintanilha NS, de Souza JCF, et al. RN, et al. Differentially expressed plasmatic microRNAs in Brazilian patients with coronavirus disease 2019 (COVID-19): preliminary results. Mol Biol Rep. 2022;49(7):6931–43.
pubmed: 35301654
pmcid: 8929466
doi: 10.1007/s11033-022-07338-9
Ma X, Liu H, Zhu J, Zhang C, Peng Y, Mao Z, et al. Mir-185-5p regulates inflammation and Phagocytosis through CDC42/JNK Pathway in macrophages. Genes (Basel). 2022;13(3):468.
pubmed: 35328023
doi: 10.3390/genes13030468
Vaz C, Ahmad HM, Sharma P, Gupta R, Kumar L, Kulshreshtha R, et al. Analysis of microRNA transcriptome by deep sequencing of small RNA libraries of peripheral blood. BMC Genomics. 2010;11(1):288.
pubmed: 20459673
pmcid: 2885365
doi: 10.1186/1471-2164-11-288
Bo L, Wei B, Wang Z, Kong D, Gao Z, Miao Z. Screening of critical genes and MicroRNAs in blood samples of patients with ruptured intracranial aneurysms by Bioinformatic Analysis of Gene Expression Data. Med Sci Monit. 2017;23:4518–25.
pubmed: 28930970
pmcid: 5618721
doi: 10.12659/MSM.902953
McLean E, Bhattarai R, Hughes BW, Mahalingam K, Bagasra O. Computational identification of mutually homologous Zika virus miRNAs that target microcephaly genes. Libyan J Med. 2017;12(1):1304505.
pubmed: 28385119
pmcid: 5418939
doi: 10.1080/19932820.2017.1304505
Lopez-Valenzuela M, Ramirez O, Rosas A, Garcia-Vargas S, de la Rasilla M, Lalueza-Fox C, et al. An ancestral miR-1304 Allele Present in neanderthals regulates genes involved in enamel formation and could explain Dental differences with modern humans. Mol Biol Evol. 2012;29(7):1797–806.
pubmed: 22319171
doi: 10.1093/molbev/mss023
Eszlari N, Petschner P, Gonda X, Baksa D, Elliott R, Anderson IM et al. Childhood Adversity Moderates the Effects of HTR2A Epigenetic Regulatory Polymorphisms on rumination. Front Psychiatry. 2019;10.
Schneider M, Debbané M, Bassett AS, Chow EWC, Fung WLA, van den Bree MBM, et al. Psychiatric disorders from Childhood to Adulthood in 22q11.2 deletion syndrome: results from the International Consortium on Brain and Behavior in 22q11.2 deletion syndrome. Am J Psychiatry. 2014;171(6):627–39.
pubmed: 24577245
pmcid: 4285461
doi: 10.1176/appi.ajp.2013.13070864
Fukata Y, Fukata M. Protein palmitoylation in neuronal development and synaptic plasticity. Nat Rev Neurosci. 2010;11(3):161–75.
pubmed: 20168314
doi: 10.1038/nrn2788
Mukai J, Liu H, Burt RA, Swor DE, Lai WS, Karayiorgou M, et al. Evidence that the gene encoding ZDHHC8 contributes to the risk of schizophrenia. Nat Genet. 2004;36(7):725–31.
pubmed: 15184899
doi: 10.1038/ng1375
Chen WY, Shi YY, Zheng YL, Zhao XZ, Zhang GJ, Chen SQ, et al. Case–control study and transmission disequilibrium test provide consistent evidence for association between schizophrenia and genetic variation in the 22q11 gene ZDHHC8. Hum Mol Genet. 2004;13(23):2991–5.
pubmed: 15489219
doi: 10.1093/hmg/ddh322
Ota VK, Gadelha A, Assunção IB, Santoro ML, Christofolini DM, Bellucco FT, et al. ZDHHC8 gene may play a role in cortical volumes of patients with schizophrenia. Schizophr Res. 2013;145(1–3):33–5.
pubmed: 23403413
doi: 10.1016/j.schres.2013.01.011
Shashi V, Francis A, Hooper SR, Kranz PG, Zapadka M, Schoch K, et al. Increased corpus callosum volume in children with chromosome 22q11.2 deletion syndrome is associated with neurocognitive deficits and genetic polymorphisms. Eur J Hum Genet. 2012;20(10):1051–7.
pubmed: 22763378
pmcid: 3449066
doi: 10.1038/ejhg.2012.138
Choi WY, Giraldez AJ, Schier AF. Target protectors reveal dampening and balancing of nodal agonist and antagonist by miR-430. Sci (1979). 2007;318(5848):271–4.
Johnston RJ, Hobert O. A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature. 2003;426(6968):845–9.
pubmed: 14685240
doi: 10.1038/nature02255
Forstner AJ, Degenhardt F, Schratt G, Nöthen MM. MicroRNAs as the cause of schizophrenia in 22q11.2 deletion carriers, and possible implications for idiopathic disease: a mini-review. Front Mol Neurosci. 2013;6.
Saunders MA, Liang H, Li WH. Human polymorphism at microRNAs and microRNA target sites. Proc Natl Acad Sci U S A. 2007;104(9):3300–5.
pubmed: 17360642
pmcid: 1805605
doi: 10.1073/pnas.0611347104
Zhao D, Wu K, Sharma S, Xing F, Wu SY, Tyagi A, et al. Exosomal mir-1304-3p promotes breast cancer progression in African americans by activating cancer-associated adipocytes. Nat Commun. 2022;13(1):7734.
pubmed: 36517516
pmcid: 9751138
doi: 10.1038/s41467-022-35305-2