In silico Analysis of Polymorphisms in microRNAs Deregulated in Alzheimer Disease

Moraghebi, Mahta; Maleki, Reza; Ahmadi, Mohsen; Negahi, Ahmad Agha; Abbasi, Hossein; Mousavi, Pegah

doi:10.3389/fnins.2021.631852

Cited by 5 publications

(7 citation statements)

References 86 publications

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“…We predicted and calculated the minimal free energies of the secondary structures of miR-3976 bounding to the CD147 3′-UTR containing T/C variant (rs6757) by computational modeling. The minimal folding energy and the ΔΔG value were used to assess the impact of SNPs on the binding ability of the miRNA with its target mRNA [ 22 ]. The minimal folding energies of the duplexes rs6757-T-containing (− 24.7 kcal/mol) is lower than that of the duplexes rs6757-C-containing (− 20.2 kcal/mol).…”

Section: Discussionmentioning

confidence: 99%

Rs6757 in microRNA-3976 binding site of CD147 confers risk of hepatocellular carcinoma in South Chinese population

Guo

Wang

et al. 2022

World J Surg Onc

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Background Cluster of differentiation 147 (CD147) overexpression plays a key role in the proliferation, differentiation, invasion, metastasis, and prognosis of hepatocellular carcinoma (HCC). The aim of this study was to explore the relationship between rs6757 and the HCC risk in the South Chinese population, and the functional significance of rs6757 by affecting the efficacy of microRNA-3976 (miR-3976) binding to the CD147 3′-UTR. Methods We performed a retrospective case-control study to analyze the association between rs6757 and the risk of HCC. We chose candidate microRNAs with the potential of interacting with rs6757 through a series of silico analyses. A luciferase reporter gene assay was implemented to detect the binding extent of microRNAs to each polymorphic allele of rs6757. Results An obvious association between rs6757 and the risk of HCC was detected in C vs. T (OR = 1.826, 95% CI [1.263–2.642]), CC vs. TT (OR = 4.513, 95% CI [1.510–13.489]), dominant genetic model (OR = 1.824, 95% CI [1.120–2.965]), and recessive genetic model (OR = 3.765, 95% CI [1.286–11.020]). Bioinformatics analysis indicated that miR-3976 binding sites containing the rs6757-T allele had lower free energies than those with the C allele, the lower free energies, the higher affinities. Luciferase activity was remarkably decreased by miR-3976 binding to the CD147 3′-UTR bearing rs6757 T allele, which could be reversed by miR-3976 inhibitors. Furthermore, miR-3976 reduced the luciferase expression in a manner of dose-dependent when cotransfected with constructs with the CD147-TT-pSICHECK2. Conclusions The research we have done suggests that rs6757 confers the CD147 allele-specific translational suppression by miR-3976, which provides a theoretical basis for antineoplastic therapy targeting CD147.

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Section: Discussionmentioning

confidence: 99%

Rs6757 in microRNA-3976 binding site of CD147 confers risk of hepatocellular carcinoma in South Chinese population

Guo

Wang

et al. 2022

World J Surg Onc

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“… 26 Generally, each miRNA can regulate various target genes and the polymorphisms in their target-binding site can have 3 outcomes, which include (1) neutral, (2) gain of novel targets, or (3) the loss of the original target. 6 , 27 Thus, a change in the binding site of miRNAs to their target genes or proteins alters the miRNA function; moreover, it alters their expression pattern by affecting the promoter area. 6 , 27 , 28 Labib et al showed that genotyping miRNA-146a polymorphism (rs2910164) and its target gene IRAK1 (rs3027898) was significantly correlated with susceptivity, clinical manifestations, and progressive condition in patients with systemic lupus erythematosus (SLE) and MS.…”

Section: Discussionmentioning

confidence: 99%

“… 6 , 27 Thus, a change in the binding site of miRNAs to their target genes or proteins alters the miRNA function; moreover, it alters their expression pattern by affecting the promoter area. 6 , 27 , 28 Labib et al showed that genotyping miRNA-146a polymorphism (rs2910164) and its target gene IRAK1 (rs3027898) was significantly correlated with susceptivity, clinical manifestations, and progressive condition in patients with systemic lupus erythematosus (SLE) and MS. Hence, it seems possible that rs2910164 polymorphism is involved in patients’ susceptibility to SLE and MS. 29 The previous publication revealed that interleukin-1 receptor–associated kinase 1 (IRAK1) could act as a potential target of miR-146a.…”

Section: Discussionmentioning

confidence: 99%

“…As it has been proved, polymorphisms in genes could probably affect the gene function, expression, splicing, stability, protein interaction, and interaction with non-coding RNAs. 6 Polymorphisms—would also influence the microRNAs -likewise genes. Muñoz-San Martín et al investigated 28 potential microRNAs in 46 patients with MS by TaqMan assays and qPCR.…”

Section: Introductionmentioning

confidence: 99%

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The Analysis of SNPs’ Function in miR-21 and miR146a/b in Multiple Sclerosis and Active Lesions: An In Silico Study

Moraghebi

Negahi

Bazireh

et al. 2022

Bioinform Biol Insights

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Multiple sclerosis (MS) is a central nervous disorder caused by several factors. Studies have recently shown that non-coding RNA such as miRNA could participate in MS initiation, progression, and active lesion. This study aims to theoretically analyze the potential impact of single-nucleotide polymorphisms (SNPs) on mir-21 and mir-146a/b, which has been previously demonstrated as MS microRNA signature. To fulfill this purpose, the SNPs were investigated for functionality through several online tools, including miRNA-SNP, SNP2-TFBS, RBP-Var, and RNAfold. Furthermore, SNPs of miR-21 and miR-146a/b that exist in pre-miRNA, mature miRNA, and promoter area were extracted; moreover, miRNA and RNA-binding protein interactions were analyzed. This article presented a list of validated SNPs that could affect the expression or function of miR-21 and miR-146a/b for the future practical study of MS and active lesions.

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“…In parallel, the development of large-scale genome wide analysis techniques has offered novel insights into the role of miRNA gene polymorphisms in the development of neurological disorders such as Tourette syndrome 21 . Mutations within a miRNA gene may affect different stages of its transcript processing and may result in abrogated miRNA function 22 . In AD, the presence of rs2910164 within MIR146A resulted in decreased levels of miR-146a-5p, correlating with increased levels of TLR-2, a critical microglial receptor mediating neuroinflammation following its binding to Aβ42 23, 24 .…”

Section: Introductionmentioning

confidence: 99%

A multi-omics approach identifies a blood-based miRNA signature of cognitive decline in two large observational trials

Sadlon

Takousis

Εvangelou

et al. 2022

Preprint

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Identifying individuals before the onset of overt symptoms is a key prerequisite for the prevention of Alzheimer's disease (AD). A wealth of data reports dysregulated microRNA (miRNA) expression in the blood of individuals with AD, but evidence in individuals at subclinical stages is sparse. In this study, a qPCR analysis of a prioritised set of 38 candidate miRNAs in the blood of 830 healthy individuals from the CHARIOT PRO cohort (West London, UK) was undertaken. Here, we identified six differentially expressed miRNAs (hsa-miR-128-3p, hsa-miR-144-5p, hsa-miR-146a-5p, hsa-miR-26a-5p, hsa-miR-29c-3p and hsa-miR-363-3p) in the blood of individuals with low cognitive performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A pathway enrichment analysis for the six miRNAs indicated involvement of apoptosis and inflammation, relevant in early AD stages. Subsequently, we used whole genome sequencing (WGS) data from 750 individuals from the AD Neuroimaging Initiative (ADNI) to perform a genetic association analysis for polymorphisms within the significant miRNAs' genes and CSF concentrations of phosphorylated-tau, total-tau, amyloid-β42 and soluble-TREM2 and BACE1 activity. Our analysis revealed 24 SNPs within MIR29C to be associated with CSF levels of amyloid-β42 and soluble-TREM2 and BACE1 activity. Our study shows the potential of a six-miRNA set as diagnostic blood biomarker of subclinical cognitive deficits in AD. Polymorphisms within MIR29C suggest a possible interplay between the amyloid cascade and microglial activation at preclinical stages of AD.

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In silico Analysis of Polymorphisms in microRNAs Deregulated in Alzheimer Disease

Cited by 5 publications

References 86 publications

Rs6757 in microRNA-3976 binding site of CD147 confers risk of hepatocellular carcinoma in South Chinese population

Rs6757 in microRNA-3976 binding site of CD147 confers risk of hepatocellular carcinoma in South Chinese population

The Analysis of SNPs’ Function in miR-21 and miR146a/b in Multiple Sclerosis and Active Lesions: An In Silico Study

A multi-omics approach identifies a blood-based miRNA signature of cognitive decline in two large observational trials

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