Downregulation of miR-185 is a common pathogenic event in 22q11.2 deletion syndrome-related and idiopathic schizophrenia

Sabaie, Hani; Gharesouran, Jalal; Asadi, Mohammad Reza; Farhang, Sara; Ahangar, Noora Karim; Brand, Serge; Arsang‐Jang, Shahram; Dastar, Saba; Taheri, Mohammad; Rezazadeh, Maryam

doi:10.1007/s11011-022-00918-5

Cited by 13 publications

(4 citation statements)

References 54 publications

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“…In the past few years, a considerable amount of research has been conducted to examine the role of miRNAs in neuropsychiatric disease [147][148][149][150][151][152][153][154][155][156]. We and other investigators have examined the expression of miRNAs in human postmortem brains of depressed subjects, in the brain of animals showing depression-like behavior, and in peripheral tissues such as blood, urine, and saliva [6,96,144,150,[157][158][159][160][161][162][163][164][165][166][167].…”

Section: Studies Of Dna Methylation In Adolescents With Elsmentioning

confidence: 99%

Dissecting early life stress-induced adolescent depression through epigenomic approach

Ochi

Dwivedi

2022

Mol Psychiatry

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Early life stress (ELS), such as abuse and neglect during childhood, can lead to psychiatric disorders in later life. Previous studies have suggested that ELS can cause profound changes in gene expression through epigenetic mechanisms, which can lead to psychiatric disorders in adulthood; however, studies on epigenetic modifications associated with ELS and psychiatric disorders in adolescents are limited. Moreover, how these epigenetic modifications can lead to psychiatric disorders in adolescents is not fully understood. Commonly, DNA methylation, histone modification, and the regulation of noncoding RNAs have been attributed to the reprogramming of epigenetic profiling associated with ELS. Although only a few studies have attempted to examine epigenetic modifications in adolescents with ELS, existing evidence suggests that there are commonalities and differences in epigenetic profiling between adolescents and adults. In addition, epigenetic modifications are sex-dependent and are influenced by the type of ELS. In this review, we have critically evaluated the current evidence on epigenetic modifications in adolescents with ELS, particularly DNA methylation and the expression of microRNAs in both preclinical models and humans. We have also clarified the impact of ELS on psychiatric disorders in adolescents to predict the development of neuropsychiatric disorders and to prevent and recover these disorders through personalized medicine.

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Section: Studies Of Dna Methylation In Adolescents With Elsmentioning

confidence: 99%

Dissecting early life stress-induced adolescent depression through epigenomic approach

Ochi

Dwivedi

2022

Mol Psychiatry

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“…Congenital heart diseases are highly prevalent in 22q11.2DS patients, ranging between 22 and 84% depending on patients’ ages [ 33 – 35 ], suggesting that the downregulation of miR-185 could be involved in the cardiac phenotypes of 22q11.2DS. miR-185 seems to be associated with schizophrenia [ 36 , 37 ], and mouse models suggested that miR-185 is one of the most downregulated miRNAs in schizophrenia-related brain regions [ 26 , 37 , 38 ]. Schizophrenia is also a highly prevalent phenotype on 22q11.2DS, with estimates suggesting that one-third of 22q11.2DS patients will have it in their adulthood [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Next-generation sequencing profiling of miRNAs in individuals with 22q11.2 deletion syndrome revealed altered expression of miR-185-5p

Dantas,

Nunes,

Nunes

et al. 2024

Hum Genomics

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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 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 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.

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“…miRNA dysregulation has been reported in patients with 22q11.2DS [23][24][25] and SCZ [26,27], but it is unclear how miRNA dysregulation in patients with 22q11.2DS may increase the risk of SCZ [28]. Moreover, miR-185, a miRNA known to be associated with SCZ, is located in the 22q11.2 region and its deletion could dysregulate gene expression and ultimately leading to SCZ [29].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic factors in the 22q11.2 deletion syndrome in relation to stress and schizophrenia

Jiao,

Demars,

Iftimovici

et al. 2024

Preprint

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Abstract22q11.2 deletion syndrome (22q11.2DS) stands out as one of the most significant risk factors for schizophrenia (SCZ), with approximately 40% of individuals with 22q11.2DS experiencing psychosis. The presence of discordant phenotypes among monozygotic twins, along with the involvement of environmental factors in the multiple-hit model hypothesis for psychosis onset, underscores the potential role of epigenetic modifications in the development of neuropsychiatric disorders among individuals with 22q11.2DS. To gain a deeper understanding of the underlying biological mechanisms, we conducted a translational study using three datasets: a genome-wide methylation dataset from peripheral blood of individuals with 22q11.2DS with or without SCZ, a microRNA expression dataset from the same cohort, and a second genome-wide methylation dataset obtained from a mouse model exploring gene-environment interactions. Human recruitment was carried out at a specialized center focusing on rare psychiatric disorders and included one pair of monozygotic twins discordant for SCZ. In the animal model, DNA extraction was performed from the prefrontal cortex among four groups : wild-type and Df(h22q11)/+ mice, with or without exposure to acute stress. This study identified alterations in DNA methylation and microRNA expression linked to the 22q11.2 deletion as well as SCZ within the context of the deletion in humans. The results were then compared to the effects of the corresponding deletion and stress in the mouse model. Notably, four genes (ZBTB20, SHANK3, GRAMD1B, XKR4) overlapped across all comparisons. Pathway analysis evealed epigenetic differences in the Wnt pathway associated with stress and SCZ within the context of the deletion. These findings support the hypothesis that the onset of SCZ in individuals with 22q11.2DS may be influenced by epigenetic mechanisms, both within and outside the implicated region, under the influence of environmental stressors. If replicated, these findings could be used to develop biomarkers for early diagnosis in del22q11 carriers and to explore new targeted therapeutic strategies.

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Downregulation of miR-185 is a common pathogenic event in 22q11.2 deletion syndrome-related and idiopathic schizophrenia

Abstract: M. (2022). Downregulation of miR-185 is a common pathogenic event in 22q11.2 deletion syndrome-related and idiopathic schizophrenia. Metabolic Brain Disease, 37(4),

Cited by 13 publications

References 54 publications

Dissecting early life stress-induced adolescent depression through epigenomic approach

Dissecting early life stress-induced adolescent depression through epigenomic approach

Next-generation sequencing profiling of miRNAs in individuals with 22q11.2 deletion syndrome revealed altered expression of miR-185-5p

Epigenetic factors in the 22q11.2 deletion syndrome in relation to stress and schizophrenia

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