The Highlighted Roles of Metabolic and Cellular Response to Stress Pathways Engaged in Circulating hsa-miR-494-3p and hsa-miR-661 in Alzheimer’s Disease

Hojati, Zohreh; Omidi, Farzaneh; Dehbashi, Moein; Soltani, Bahram Mohammad

doi:10.29252/ibj.25.1.62

Cited by 13 publications

(6 citation statements)

References 31 publications

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“…The brain meta-analyses revealed hsa-miR-767-5p as commonly overexpressed in female and male AD patients, in agreement with a previous report suggesting this miRNA as a biomarker candidate in the cerebrospinal fluid of AD patients [79]. No significantly deregulated miRNAs identified in female AD patients had previously reported links to AD except hsa-miR-494, which functions in stress pathways in AD [80]. The gene targets of affected miRNAs included the MDM2 gene, which regulates p53 degradation and has previously reported links to AD [81].…”

Section: Brain Meta-analysessupporting

confidence: 90%

“…The intersection of these results revealed miR-767-5p commonly overexpressed in females and males with AD, supporting a previous report that suggested it as a biomarker candidate in the cerebrospinal fluid of AD patients [71]. Regarding sex-specific results, in females none of the significantly deregulated miRNAs reported have been previously linked to AD, except the miR-494, involved in stress pathways in AD [72]. In males, miR-7-5p was underexpressed in AD patients, contrasting with a previous study that reported an increased expression linked to NLRP3 inflammasome [73].…”

Section: Brain Meta-analysessupporting

confidence: 87%

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The role of microRNAs in understanding sex-based differences in Alzheimer’s disease

Llera-Oyola,

Carceller,

Andreu

et al. 2023

Preprint

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Background: Alzheimer's disease (AD) is the most frequent cause of dementia and its incidence is expected to rise as the life expectancy of the population increases. Sex-based differences in AD development have been described, although there are still uncertainties on the role of biological sex in molecular mechanisms of the disease. The study of sex-specific expression profiles of regulatory elements, such as microRNAs (miRNAs), could contribute to a more accurate diagnosis and treatment of the disease. Methods: We conducted a systematic review identifying five studies of microRNA expression in AD that incorporated the biological sex of the samples published in the Gene Expression Omnibus (GEO) repository. Differential expression analyses were performed for each study, considering both disease and biological sex of patients. Subsequently, results were integrated with a meta-analysis methodology. Finally, functional enrichment of the meta-analyses results was performed to establish an association between altered miRNA expression and relevant terms of the Gene Ontology (GO). Results: Meta-analyses of miRNAs expression in blood samples revealed 16 and 22 miRNAs altered in females and males, respectively. Moreover, 9 miRNAs were commonly overexpressed in both sexes, unveiling common miRNAs dysregulation profiles. In contrast, functional enrichment revealed sex-differences in biological processes altered. In males, most of the affected processes were related to ubiquitination, regulation of different kinase activities and apoptotic processes; but in females were linked to RNA splicing and translation. Meta-analyses of brain samples also revealed some alterations in miRNAs expression (6 in females and 4 in males). The unique miRNA altered in both sexes (miR-767-5p) was underexpressed in both males and females. Nonetheless, the functional enrichment analysis did not reveal any affected biological process. Conclusions: Sex-specific meta-analyses allowed for the detection of differentially expressed miRNAs in females and males. Identification of deregulated miRNAs highlighted the relevance of the sex information in biomedical data. Further studies centered on miRNA regulation should meet criteria for comparability and standardization of information.

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Section: Brain Meta-analysessupporting

confidence: 90%

Section: Brain Meta-analysessupporting

confidence: 87%

The role of microRNAs in understanding sex-based differences in Alzheimer’s disease

Llera-Oyola,

Carceller,

Andreu

et al. 2023

Preprint

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“…Thus, we aimed to explore the miRNA interacting with hub genes, most of which had the opposite expression profile of their target genes in AD. For example, miR-6740–3p, which interacts with CCT2 , is significantly upregulated in AD (logFC = 0.38540845, p = 2.34E-16) and miR-661, which interacts with HPCAL4 , NECAP1 , CLTA , and GNAI2 , has been observed to be involved in AD via metabolic and stress pathways ( Hojati et al, 2021 ). The miR-501–3p, which interacts with CADM2 , may impact AD by regulating cell division ( Hara et al, 2017 ); hsa-miR-107, which interacts with ACTR2 , AMPH , and RAN , targets Aβ precursor protein (APP) and influences AD ( Hébert et al, 2008 ).…”

Section: Discussionmentioning

confidence: 99%

Multi-omics analysis revealed the role of CCT2 in the induction of autophagy in Alzheimer’s disease

Feng

Quan

et al. 2023

Front. Genet.

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Chaperonin containing TCP1 subunit 2 (CCT2) is essential in various neurodegenerative diseases, albeit its role in the pathogenesis of Alzheimer’s disease (AD) remains elusive. This study aimed to evaluate the role of CCT2 in Alzheimer’s disease. First, bioinformatics database analysis revealed that CCT2 was significantly downregulated in patients with Alzheimer’s disease and associated with autophagic clearance of β-amyloid. The 789 differentially expressed genes overlapped in AD-group and CCT2-low/high group, and the CCT2-high-associated genes screened by Pearson coefficients were enriched in protein folding, autophagy, and messenger RNA stability regulation pathways. These results suggest that CCT2 is significantly and positively associated with multiple pathways linked to autophagy and negatively associated with neuronal death. The logistic prediction model with 13 key genes, such as CCT2, screened in this study better predicts Alzheimer’s disease occurrence (AUC = 0.9671) and is a favorable candidate for predicting potential biological targets of Alzheimer’s disease. Additionally, this study predicts reciprocal micro RNAs and small molecule drugs for hub genes. Our findings suggest that low CCT2 expression may be responsible for the autophagy suppression in Alzheimer’s disease, providing an accurate explanation for its pathogenesis and new targets and small molecule inhibitors for its treatment.

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“…A neuroprotective role of hsa-miR-103a-3p inhibition in Parkinson’s disease has been demonstrated previously [ 71 ]. For hsa-miR-494-3p, alterations in expression have been linked to neurodegenerative disease, including Alzheimer’s disease and Parkinson’s disease, and malignant brain tumors, such as glioma, glioblastoma, and medulloblastoma [ 72 , 73 , 74 , 75 , 76 ]. The potential role of hsa-miR-103a-3p and hsa-miR-494-3p in neurodevelopmental pathologies, such as TSC, has not yet been described, despite hsa-miR-494-3 having been described as a key regulator of endometrial receptivity through the PI3K/AKT/mTOR pathway [ 77 ].…”

Section: Discussionmentioning

confidence: 99%

miRNAs and isomiRs: Serum-Based Biomarkers for the Development of Intellectual Disability and Autism Spectrum Disorder in Tuberous Sclerosis Complex

et al. 2022

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Tuberous sclerosis complex (TSC) is a rare multi-system genetic disorder characterized by a high incidence of epilepsy and neuropsychiatric manifestations known as tuberous-sclerosis-associated neuropsychiatric disorders (TANDs), including autism spectrum disorder (ASD) and intellectual disability (ID). MicroRNAs (miRNAs) are small regulatory non-coding RNAs that regulate the expression of more than 60% of all protein-coding genes in humans and have been reported to be dysregulated in several diseases, including TSC. In the current study, RNA sequencing analysis was performed to define the miRNA and isoform (isomiR) expression patterns in serum. A Receiver Operating Characteristic (ROC) curve analysis was used to identify circulating molecular biomarkers, miRNAs, and isomiRs, able to discriminate the development of neuropsychiatric comorbidity, either ASD, ID, or ASD + ID, in patients with TSC. Part of our bioinformatics predictions was verified with RT-qPCR performed on RNA isolated from patients’ serum. Our results support the notion that circulating miRNAs and isomiRs have the potential to aid standard clinical testing in the early risk assessment of ASD and ID development in TSC patients.

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The Highlighted Roles of Metabolic and Cellular Response to Stress Pathways Engaged in Circulating hsa-miR-494-3p and hsa-miR-661 in Alzheimer’s Disease

Cited by 13 publications

References 31 publications

The role of microRNAs in understanding sex-based differences in Alzheimer’s disease

The role of microRNAs in understanding sex-based differences in Alzheimer’s disease

Multi-omics analysis revealed the role of CCT2 in the induction of autophagy in Alzheimer’s disease

miRNAs and isomiRs: Serum-Based Biomarkers for the Development of Intellectual Disability and Autism Spectrum Disorder in Tuberous Sclerosis Complex

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