Identification of serum microRNA signatures associated with autism spectrum disorder as promising candidate biomarkers

Kichukova, Tatyana M.; Petrov, Veselin; Popov, Nikolay T.; Minchev, D.; Naimov, Samir; Minkov, Ivan; Vachev, Tihomir

doi:10.1016/j.heliyon.2021.e07462

Cited by 7 publications

(7 citation statements)

References 72 publications

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“…Considering all included studies, a range of data elements were used to capture ncRNA gene differential expression. Only 17 papers included both fold change and associated statistical findings [ 43 , 73 , 75 , 77 , 78 , 80 – 82 , 85 , 90 , 101 – 103 , 110 , 113 , 114 , 117 ] and often the latter was not corrected for multiple testing. The different data types, levels of data processing and in many instances inaccessible data, made meta-analysis unsuitable [ 118 ].…”

Section: Resultsmentioning

confidence: 99%

“…For example, the use of an EDTA anticoagulant appears to influence specific miRNA expression, particularly after longer EDTA exposure times [ 196 ]. In our systematic review, EDTA blood tubes were used in several studies [ 73 , 75 , 76 , 89 , 90 , 93 , 101 , 105 ] with only a few studies using PAXgene blood RNA tubes [ 94 , 102 , 104 , 110 ] and many studies omitted details about blood sample collection, including anticoagulant exposure timings. Quantity and quality of centrifuging in blood has also been shown to alter the proportion of intra and extracellular components that may demonstrate different miRNA expression properties [ 197 ].…”

Section: Discussionmentioning

confidence: 99%

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A systematic review of non-coding RNA genes with differential expression profiles associated with autism spectrum disorders

et al. 2023

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Aims To identify differential expression of shorter non-coding RNA (ncRNA) genes associated with autism spectrum disorders (ASD). Background ncRNA are functional molecules that derive from non-translated DNA sequence. The HUGO Gene Nomenclature Committee (HGNC) have approved ncRNA gene classes with alignment to the reference human genome. One subset is microRNA (miRNA), which are highly conserved, short RNA molecules that regulate gene expression by direct post-transcriptional repression of messenger RNA. Several miRNA genes are implicated in the development and regulation of the nervous system. Expression of miRNA genes in ASD cohorts have been examined by multiple research groups. Other shorter classes of ncRNA have been examined less. A comprehensive systematic review examining expression of shorter ncRNA gene classes in ASD is timely to inform the direction of research. Methods We extracted data from studies examining ncRNA gene expression in ASD compared with non-ASD controls. We included studies on miRNA, piwi-interacting RNA (piRNA), small NF90 (ILF3) associated RNA (snaR), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), transfer RNA (tRNA), vault RNA (vtRNA) and Y RNA. The following electronic databases were searched: Cochrane Library, EMBASE, PubMed, Web of Science, PsycINFO, ERIC, AMED and CINAHL for papers published from January 2000 to May 2022. Studies were screened by two independent investigators with a third resolving discrepancies. Data was extracted from eligible papers. Results Forty-eight eligible studies were included in our systematic review with the majority examining miRNA gene expression alone. Sixty-four miRNA genes had differential expression in ASD compared to controls as reported in two or more studies, but often in opposing directions. Four miRNA genes had differential expression in the same direction in the same tissue type in at least 3 separate studies. Increased expression was reported in miR-106b-5p, miR-155-5p and miR-146a-5p in blood, post-mortem brain, and across several tissue types, respectively. Decreased expression was reported in miR-328-3p in bloods samples. Seven studies examined differential expression from other classes of ncRNA, including piRNA, snRNA, snoRNA and Y RNA. No individual ncRNA genes were reported in more than one study. Six studies reported differentially expressed snoRNA genes in ASD. A meta-analysis was not possible because of inconsistent methodologies, disparate tissue types examined, and varying forms of data presented. Conclusion There is limited but promising evidence associating the expression of certain miRNA genes and ASD, although the studies are of variable methodological quality and the results are largely inconsistent. There is emerging evidence associating differential expression of snoRNA genes in ASD. It is not currently possible to say whether the reports of differential expression in ncRNA may relate to ASD aetiology, a response to shared environmental factors linked to ASD such as sleep and nutrition, other molecular functions, human diversity, or chance findings. To improve our understanding of any potential association, we recommend improved and standardised methodologies and reporting of raw data. Further high-quality research is required to shine a light on possible associations, which may yet yield important information.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A systematic review of non-coding RNA genes with differential expression profiles associated with autism spectrum disorders

et al. 2023

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“…MicroRNAs (miRNAs), small RNAs approximately 19–23 nucleotides long with complementarity to specific regions in messenger RNAs (mRNAs), are key regulators of gene expression via binding of miRNAs to target mRNAs, which could trigger the cleavage, translational repression, or deadenylation of these targets, miRNAs regulate gene expression at the post-transcriptional level and are playing a key role in coordinating nervous system development and neuronal function in the mature brain. [ 14 , 15 ] It is commonly accepted that a linkage between altered miRNAs and risk of neuropsychiatric disorders has been established. Recent studies have revealed that aberrant levels of miRNAs are present in the peripheral blood of patients with neuropsychiatric disorders, such as SZ, MDD, GAD.…”

Section: Introductionmentioning

confidence: 99%

Differentiation value of miR-26b for major depressive disorder, schizophrenia, generalized anxiety disorder

Kong

Zhu

Zhang

et al. 2023

Indian Journal of Psychiatry

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Introduction: First episode and drug naive schizophrenia (SZ) patients comorbid with major depressive episode and generalized anxiety disorder (GAD) comorbid with major depressive disorder (MDD) are common in clinical practice, overlapping symptomatology during first presentation of MDD, SZ and GAD challenged the diagnostic process. Materials and Methods: This study aimed to investigate the differentiation value of peripheral microRNA-26b expression in 52 patients of MDD, SZ, and GAD, respectively, and 52 controls. Quantitative real-time reverse transcription polymerase chain reaction was used to further verify aberrant miRNAs of previous identified in MDD and investigate expression level of these peripheral miRNAs in SZ and GAD. Results: The expression levels of miR-26b and miR-4743 were significantly upregulated and of miR-4498, miR-4485, and miR-1972 had no significant difference. There were no significant differences of expression levels of miR-26b, miR-4498, miR-4485, and miR-1972 except miR-4743 between SZ patients and control group and of miR-26b, miR-1972, miR-4498, and miR-4485 between GAD group and the controls. The receiver operating characteristic (ROC) curve of miR-26b in MDD patients showed that its sensitivity and specificity for diagnosis were 0.540 and 0.830, respectively, with the area under curve (AUC) being 0.728; the ROC of miR-26b for SZ and MDD differentiation showed that its sensitivity and specificity were 0.580 and 0.710, respectively, with AUC being 0.631; the ROC of miR-26b for GAD and MDD differentiation suggested that sensitivity and specificity were 0.560 and 0.750, respectively, with AUC being 0.637. Conclusion: MiR-26b might have potential value of differentiation biomarker for MDD, SZ, and GAD.

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“…Altered expression of cellular and circulating miRNAs has been observed in ASD individuals compared with typically developing (TD) controls, and they are now considered as potential targets for the development of ASD novel therapeutic strategies [15,16]. In particular, dysregulation of some miRNAs (miR-197-5p, miR-424-5p, miR-500a-5p, miR-664a-5p) is associated with ASD and these molecules can potentially constitute molecular biomarkers [17], whereas other miRNAs (miR-21-5p, miR-320a-5p, miR-31-5p, miR-223-5p) may serve as important causative factors of different gastrointestinal disorders [18].…”

Section: Introductionmentioning

confidence: 99%

Expression of miRNAs in Pre-Schoolers with Autism Spectrum Disorders Compared with Typically Developing Peers and Its Effects after Probiotic Supplementation

Guiducci,

Cabiati,

Santocchi

et al. 2023

JCM

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Alteration of the microbiota–gut–brain axis has been recently recognized as a possible contributor to the physiopathology of autism spectrum disorder (ASD). In this context, microRNA (miRNAs) dysfunction, implicated both in several neuropathological conditions including ASD and in different gastrointestinal disorders (GIDs), could represent an important modulating factor. In this contextual framework, we studied the transcriptional profile of specific circulating miRNAs associated with both ASD (miR-197-5p, miR-424-5p, miR-500a-5p, miR-664a-5p) and GID (miR-21-5p, miR-320a-5p, miR-31-5p, miR-223-5p) in a group of pre-schoolers with ASD and in typically developing (TD) peers. In the ASD group, we also assessed the same miRNAs after a 6-month supplementation with probiotics and their correlation with plasma levels of zonulin and lactoferrin. At baseline, the expression of miRNAs involved in ASD were significantly reduced in ASD pre-schoolers vs. TD controls. Regarding the miRNAs involved in GID, the expression levels of miR-320-5p, miR-31-5p, and miR-223-5p were significantly higher in ASD than in TD subjects, whereas miR-21-5p showed significantly reduced expression in the ASD group vs. TD group. Supplementation with probiotics did not significantly change the expression of miRNAs in the ASD population. We found a significative negative correlation between zonulin and miR-197-5p and miR-21-5p at baseline, as well as between lactoferrin and miR-223-5p after 6 months of probiotic supplementation. Our study confirms the presence of an altered profile of the miRNAs investigated in ASD versus TD peers that was not modified by supplementation with probiotics.

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Identification of serum microRNA signatures associated with autism spectrum disorder as promising candidate biomarkers

Cited by 7 publications

References 72 publications

A systematic review of non-coding RNA genes with differential expression profiles associated with autism spectrum disorders

A systematic review of non-coding RNA genes with differential expression profiles associated with autism spectrum disorders

Differentiation value of miR-26b for major depressive disorder, schizophrenia, generalized anxiety disorder

Expression of miRNAs in Pre-Schoolers with Autism Spectrum Disorders Compared with Typically Developing Peers and Its Effects after Probiotic Supplementation

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