Identification of Peripheral Blood miRNA Biomarkers in First-Episode Drug-Free Schizophrenia Patients Using Bioinformatics Strategy

Jin, Mengdi; Zhu, Xiaojing; Sun, Yaoyao; Li, Zhijun; Li, Xinwei; Ai, Lizhe; He, Yang; Liu, Yane; Jia, Ningning; Hu, Guoyan; Cui, Xueling; Xie, Mengtong; Yang, Yuqing; Yu, Qiong

doi:10.1007/s12035-022-02878-4

Cited by 14 publications

(5 citation statements)

References 86 publications

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“…The fact that this microRNA is widely expressed in the hippocampus and various cortical areas [35] implies that hsa-miR-1185-1-3p might regulate GDNF expression in the brain, and individuals possessing the 'G' risk allele express lower amounts of GDNF levels, rendering them more vulnerable to the disease as early as during embryonic development, a critical period according to the neurodevelopmental hypothesis of schizophrenia. Although dozens of miRNAs have been proposed to be differentially expressed in schizophrenia [54], this is the first study implicating hsa-miR-1185-1-3p in the disease with a functional role mediated by a binding site polymorphism.…”

Section: Discussionmentioning

confidence: 92%

MicroRNA-Mediated Suppression of Glial Cell Line-Derived Neurotrophic Factor Expression Is Modulated by a Schizophrenia-Associated Non-Coding Polymorphism

Keszler,

Vékony,

Elek

et al. 2024

IJMS

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Plasma levels of glial cell line-derived neurotrophic factor (GDNF), a pivotal regulator of differentiation and survival of dopaminergic neurons, are reportedly decreased in schizophrenia. To explore the involvement of GDNF in the pathogenesis of the disease, a case–control association analysis was performed between five non-coding single nucleotide polymorphisms (SNP) across the GDNF gene and schizophrenia. Of them, the ‘G’ allele of the rs11111 SNP located in the 3′ untranslated region (3′-UTR) of the gene was found to associate with schizophrenia. In silico analysis revealed that the rs11111 ‘G’ allele might create binding sites for three microRNA (miRNA) species. To explore the significance of this polymorphism, transient co-transfection assays were performed in human embryonic kidney 293T (HEK293T) cells with a luciferase reporter construct harboring either the ‘A’ or ‘G’ allele of the 3′-UTR of GDNF in combination with the hsa-miR-1185-1-3p pre-miRNA. It was demonstrated that in the presence of the rs11111 ‘G’ (but not the ‘A’) allele, hsa-miR-1185-2-3p repressed luciferase activity in a dose-dependent manner. Deletion of the miRNA binding site or its substitution with the complementary sequence abrogated the modulatory effect. Our results imply that the rs11111 ‘G’ allele occurring more frequently in patients with schizophrenia might downregulate GDNF expression in a miRNA-dependent fashion.

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Section: Discussionmentioning

confidence: 92%

MicroRNA-Mediated Suppression of Glial Cell Line-Derived Neurotrophic Factor Expression Is Modulated by a Schizophrenia-Associated Non-Coding Polymorphism

Keszler,

Vékony,

Elek

et al. 2024

IJMS

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“…Altered miR-144-3p expression has been noted in various samples from individuals with ASD, including brain tissue, serum, and peripheral blood [ 50 , 65 , 66 ], as well as in the peripheral blood of individuals with SCZ [ 67 ]. In this case, the treatment did not affect its levels and no remarkable differences were observed between sexes ( Figure 3 C).…”

Section: Resultsmentioning

confidence: 99%

Exploratory Analysis of MicroRNA Alterations in a Neurodevelopmental Mouse Model for Autism Spectrum Disorder and Schizophrenia

García-Cerro,

Gómez-Garrido,

Garcia

et al. 2024

IJMS

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MicroRNAs (miRNAs) play a crucial role in the regulation of gene expression levels and have been implicated in the pathogenesis of autism spectrum disorder (ASD) and schizophrenia (SCZ). In this study, we examined the adult expression profiles of specific miRNAs in the prefrontal cortex (PFC) of a neurodevelopmental mouse model for ASD and SCZ that mimics perinatal pathology, such as NMDA receptor hypofunction, and exhibits behavioral and neurophysiological phenotypes related to these disorders during adulthood. To model the early neuropathogenesis of the disorders, mouse pups were administered subcutaneously with ketamine (30 mg/Kg) at postnatal days 7, 9, and 11. We focused on a set of miRNAs most frequently altered in ASD (miR-451a and miR-486-3p) and in SCZ (miR-132-3p and miR-137-3p) according to human studies. Additionally, we explored miRNAs whose alterations have been identified in both disorders (miR-21-5p, miR-92a-2-5p, miR-144-3p, and miR-146a-5p). We placed particular emphasis on studying the sexual dimorphism in the dynamics of these miRNAs. Our findings revealed significant alterations in the PFC of this ASD- and SCZ-like mouse model. Specifically, we observed upregulated miR-451a and downregulated miR-137-3p. Furthermore, we identified sexual dimorphism in the expression of miR-132-3p, miR-137-3p, and miR-92a-2-5p. From a translational perspective, our results emphasize the potential involvement of miR-92a-2-5p, miR-132-3p, miR-137-3p, and miR-451a in the pathophysiology of ASD and SCZ and strengthen their potential as biomarkers and therapeutic targets of such disorders.

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“…In our meta-analysis, we focused on differentially expressed miRNAs derived from peripheral blood, excluding studies from brain tissue, as the method for extracting miRNAs from brain tissue has limited sample sources and are difficult to apply in clinical practice. Studies have found that brain disease-specific miRNAs can also be detected in peripheral blood, where their levels were highly correlated with those in the brain (96,97). Interestingly, in SZ patients, miR-181b-5p and miR-132-3p were significantly increased in the pooled results, but only in certain blood elements in subgroup analysis based on specimen type.…”

Section: Discussionmentioning

confidence: 95%

Identifying the differentially expressed peripheral blood microRNAs in psychiatric disorders: a systematic review and meta-analysis

Liu,

Dong,

Jiang

et al. 2024

Front. Psychiatry

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BackgroundEvidence has suggested that microRNAs (miRNAs) may play an important role in the pathogenesis of psychiatric disorders (PDs), but the results remain inconclusive. We aimed to identify specific differentially expressed miRNAs and their overlapping miRNA expression profiles in schizophrenia (SZ), major depression disorder (MDD), and bipolar disorder (BD), the three major PDs.MethodsThe literatures up to September 30, 2023 related to peripheral blood miRNAs and PDs were searched and screened from multiple databases. The differences in miRNA levels between groups were illustrated by the standardized mean difference (SMD) and 95% confidence interval (95% CI).ResultsIn total, 30 peripheral blood miRNAs were included in the meta-analysis, including 16 for SZ, 12 for MDD, and 2 for BD, each was reported in more than 3 independent studies. Compared with the control group, miR-181b-5p, miR-34a-5p, miR-195-5p, miR-30e-5p, miR-7-5p, miR-132-3p, miR-212-3p, miR-206, miR-92a-3p and miR-137-3p were upregulated in SZ, while miR-134-5p, miR-107 and miR-99b-5p were downregulated. In MDD, miR-124-3p, miR-132-3p, miR-139-5p, miR-182-5p, miR-221-3p, miR-34a-5p and miR-93-5p were upregulated, while miR-144-5p and miR-135a-5p were downregulated. However, we failed to identify statistically differentially expressed miRNAs in BD. Interestingly, miR-132-3p and miR-34a-5p were upregulated in both SZ and MDD.ConclusionsOur study identified 13 differentially expressed miRNAs in SZ and 9 in MDD, among which miR-132-3p and miR-34a-5p were upregulated in both SZ and MDD by systematically analyzing qualified studies. These miRNAs may be used as potential biomarkers for the diagnosis of SZ and MDD in the future.Systematic Review Registrationhttp://www.crd.york.ac.uk/PROSPERO, identifier CRD42023486982.

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Identification of Peripheral Blood miRNA Biomarkers in First-Episode Drug-Free Schizophrenia Patients Using Bioinformatics Strategy

Cited by 14 publications

References 86 publications

MicroRNA-Mediated Suppression of Glial Cell Line-Derived Neurotrophic Factor Expression Is Modulated by a Schizophrenia-Associated Non-Coding Polymorphism

MicroRNA-Mediated Suppression of Glial Cell Line-Derived Neurotrophic Factor Expression Is Modulated by a Schizophrenia-Associated Non-Coding Polymorphism

Exploratory Analysis of MicroRNA Alterations in a Neurodevelopmental Mouse Model for Autism Spectrum Disorder and Schizophrenia

Identifying the differentially expressed peripheral blood microRNAs in psychiatric disorders: a systematic review and meta-analysis

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