Implications of SNP-triggered MiRNA Dysregulation in Schizophrenia Development

Overview

Journal Front Genet

Date 2024 Feb 12

PMID 38343691

Authors

Fadumo Abdullahi Mohamed

Kristine Freude

Affiliations

Soon will be listed here.

Abstract

This review examines the substantial involvement of Single Nucleotide Polymorphisms (SNPs) and microRNAs (miRNAs) in the etiology and susceptibility to Schizophrenia, with particular emphasis on the dopaminergic, glutamatergic, and GABAergic systems. It elucidates the potential of SNPs to disrupt miRNA-mRNA interactions, leading to alterations in the regulatory mechanisms of Schizophrenia risk genes and subsequently influencing the susceptibility to Schizophrenia. Specific attention is given to the impact of SNPs in , and , as well as the potential for changes in gene expression driven by miR-9 and miR-326, heightening the likelihood of Schizophrenia development. Furthermore, the review explores genetic alterations in the glutamatergic system, focusing on modifications linked to and its associated miRNAs, which have been reported to have a notable impact on the occurrence of Schizophrenia. Knowledge of the involvement of SNPs within miRNAs in influencing the expression of essential genes within the GABA system are emerging and described in this review, including their potential consequences for Schizophrenia.

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References

Shorter K, Miller B . Epigenetic mechanisms in schizophrenia. Prog Biophys Mol Biol. 2015; 118(1-2):1-7. PMC: 4631256. DOI: 10.1016/j.pbiomolbio.2015.04.008. View

Chen X, Zhang Z, Zhang Q, Zhao W, Zhai J, Chen M . Effect of rs1344706 in the gene on the brain network. Neuroimage Clin. 2018; 17:1000-1005. PMC: 5842752. DOI: 10.1016/j.nicl.2017.12.017. View

Sood P, Krek A, Zavolan M, Macino G, Rajewsky N . Cell-type-specific signatures of microRNAs on target mRNA expression. Proc Natl Acad Sci U S A. 2006; 103(8):2746-51. PMC: 1413820. DOI: 10.1073/pnas.0511045103. View

Channakkar A, Singh T, Pattnaik B, Gupta K, Seth P, Adlakha Y . MiRNA-137-mediated modulation of mitochondrial dynamics regulates human neural stem cell fate. Stem Cells. 2020; 38(5):683-697. PMC: 7217206. DOI: 10.1002/stem.3155. View

Oda Y, Kanahara N, Iyo M . Alterations of Dopamine D2 Receptors and Related Receptor-Interacting Proteins in Schizophrenia: The Pivotal Position of Dopamine Supersensitivity Psychosis in Treatment-Resistant Schizophrenia. Int J Mol Sci. 2015; 16(12):30144-63. PMC: 4691170. DOI: 10.3390/ijms161226228. View

Balan S, Yamada K, Iwayama Y, Hashimoto T, Toyota T, Shimamoto C . Comprehensive association analysis of 27 genes from the GABAergic system in Japanese individuals affected with schizophrenia. Schizophr Res. 2017; 185:33-40. DOI: 10.1016/j.schres.2017.01.003. View

Zhang Z, Yan T, Wang Y, Zhang Q, Zhao W, Chen X . Polymorphism in schizophrenia risk gene is associated with the posterior cingulate Cortex's activation and functional and structural connectivity in healthy controls. Neuroimage Clin. 2018; 19:160-166. PMC: 6051762. DOI: 10.1016/j.nicl.2018.03.039. View

Beveridge N, Tooney P, Carroll A, Gardiner E, Bowden N, Scott R . Dysregulation of miRNA 181b in the temporal cortex in schizophrenia. Hum Mol Genet. 2008; 17(8):1156-68. DOI: 10.1093/hmg/ddn005. View

Rani V, Sengar R . Biogenesis and mechanisms of microRNA-mediated gene regulation. Biotechnol Bioeng. 2022; 119(3):685-692. DOI: 10.1002/bit.28029. View

10.

Warburton A, Breen G, Bubb V, Quinn J . A GWAS SNP for Schizophrenia Is Linked to the Internal MIR137 Promoter and Supports Differential Allele-Specific Expression. Schizophr Bull. 2015; 42(4):1003-8. PMC: 4903043. DOI: 10.1093/schbul/sbv144. View

11.

Hojlo M, Ghebrelul M, Genetti C, Smith R, Rockowitz S, Deaso E . Children with Early-Onset Psychosis Have Increased Burden of Rare Variants. Genes (Basel). 2023; 14(4). PMC: 10138040. DOI: 10.3390/genes14040779. View

12.

Zou M, Li D, Lv R, Zhou Y, Wang T, Liu J . Association between two single nucleotide polymorphisms at corresponding microRNA and schizophrenia in a Chinese population. Mol Biol Rep. 2011; 39(4):3385-91. DOI: 10.1007/s11033-011-1109-3. View

13.

Hu W, MacDonald M, Elswick D, Sweet R . The glutamate hypothesis of schizophrenia: evidence from human brain tissue studies. Ann N Y Acad Sci. 2014; 1338:38-57. PMC: 4363164. DOI: 10.1111/nyas.12547. View

14.

Doehring A, Kirchhof A, Lotsch J . Genetic diagnostics of functional variants of the human dopamine D2 receptor gene. Psychiatr Genet. 2009; 19(5):259-68. DOI: 10.1097/YPG.0b013e32832d0941. View

15.

Peritogiannis V, Ninou A, Samakouri M . Mortality in Schizophrenia-Spectrum Disorders: Recent Advances in Understanding and Management. Healthcare (Basel). 2022; 10(12). PMC: 9777663. DOI: 10.3390/healthcare10122366. View

16.

Haas U, Sczakiel G, Laufer S . MicroRNA-mediated regulation of gene expression is affected by disease-associated SNPs within the 3'-UTR via altered RNA structure. RNA Biol. 2012; 9(6):924-37. PMC: 3495750. DOI: 10.4161/rna.20497. View

17.

Benjamin K, Chen Q, Jaffe A, Stolz J, Collado-Torres L, Huuki-Myers L . Analysis of the caudate nucleus transcriptome in individuals with schizophrenia highlights effects of antipsychotics and new risk genes. Nat Neurosci. 2022; 25(11):1559-1568. PMC: 10599288. DOI: 10.1038/s41593-022-01182-7. View

18.

Abdelfattah A, Park C, Choi M . Update on non-canonical microRNAs. Biomol Concepts. 2014; 5(4):275-87. PMC: 4343302. DOI: 10.1515/bmc-2014-0012. View

19.

Nguyen L, Fregeac J, Bole-Feysot C, Cagnard N, Iyer A, Anink J . Role of in neural stem cell differentiation and neural lineage determination: relevance for neurodevelopmental disorders. Mol Autism. 2018; 9:38. PMC: 6011198. DOI: 10.1186/s13229-018-0219-3. View

20.

Zhang D, Li H, Ding K, Zhang Z, Luo S, Li G . Polymorphisms in MicroRNA Genes Associated with Schizophrenia Susceptibility but Not with Effectiveness of MECT. Comput Math Methods Med. 2021; 2021:1959172. PMC: 8687787. DOI: 10.1155/2021/1959172. View