APP intracellular domain acts as a transcriptional regulator of miR-663 suppressing neuronal differentiation

Shu, Riyang; Wong, Winnie; Ma, Quanhong; Yang, Zara Zhuyun; Zhu, Haifeng; Liu, F J; Wang, Ping; Ma, Jun; Yan, Shuhua; Polo, José M.; Bernard, Claude Charles Andre; Stanton, Lawrence W.; Dawe, Gavin S.; Xiao, Zhi‐Cheng

doi:10.1038/cddis.2015.10

Cited by 50 publications

(33 citation statements)

References 62 publications

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“…There is no previous report on the functions of hsa-miR-3648. A recent report stated that hsa-miR-3648 is transcriptionally regulated in neural stem cells by the amyloid precursor protein (APP)derived cleavage product, APP intracellular domain (AICD) (18). Taken together with our results indicating that hsa-miR-3648 is directly regulated by LMO1, we can suggest that AICD may cooperatively regulate the expression of hsa-miR-3648 with LMO1 in NB cells.…”

Section: Discussionsupporting

confidence: 82%

Indirect Down-regulation of Tumor-suppressivelet-7Family MicroRNAs byLMO1in Neuroblastoma

Saeki

Saito

Sugaya

et al. 2018

Cancer Genomics Proteomics

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Section: Discussionsupporting

confidence: 82%

Indirect Down-regulation of Tumor-suppressivelet-7Family MicroRNAs byLMO1in Neuroblastoma

Saeki

Saito

Sugaya

et al. 2018

Cancer Genomics Proteomics

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“…Both share an inhibitory effect on CDK6. In fact, neuronal differentiation after the neurogenesis process could result more inhibited in women compared to men, because of the lack of activation of PAX6 by CDK6 (Shu et al, 2015 ). The down-regulation of FBXL18 by miR-663A also contributes to this effect.…”

Section: Resultsmentioning

confidence: 99%

Sexual Dimorphism and Aging in the Human Hyppocampus: Identification, Validation, and Impact of Differentially Expressed Genes by Factorial Microarray and Network Analysis

Guebel¹,

Torres

2016

Front. Aging Neurosci.

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Motivation: In the brain of elderly-healthy individuals, the effects of sexual dimorphism and those due to normal aging appear overlapped. Discrimination of these two dimensions would powerfully contribute to a better understanding of the etiology of some neurodegenerative diseases, such as “sporadic” Alzheimer.Methods: Following a system biology approach, top-down and bottom-up strategies were combined. First, public transcriptome data corresponding to the transition from adulthood to the aging stage in normal, human hippocampus were analyzed through an optimized microarray post-processing (Q-GDEMAR method) together with a proper experimental design (full factorial analysis). Second, the identified genes were placed in context by building compatible networks. The subsequent ontology analyses carried out on these networks clarify the main functionalities involved.Results: Noticeably we could identify large sets of genes according to three groups: those that exclusively depend on the sex, those that exclusively depend on the age, and those that depend on the particular combinations of sex and age (interaction). The genes identified were validated against three independent sources (a proteomic study of aging, a senescence database, and a mitochondrial genetic database). We arrived to several new inferences about the biological functions compromised during aging in two ways: by taking into account the sex-independent effects of aging, and considering the interaction between age and sex where pertinent. In particular, we discuss the impact of our findings on the functions of mitochondria, autophagy, mitophagia, and microRNAs.Conclusions: The evidence obtained herein supports the occurrence of significant neurobiological differences in the hippocampus, not only between adult and elderly individuals, but between old-healthy women and old-healthy men. Hence, to obtain realistic results in further analysis of the transition from the normal aging to incipient Alzheimer, the features derived from the sexual dimorphism in hippocampus should be explicitly considered.

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“…Interestingly Fbxl18 has been identified as a direct target of APP , inhibiting neuronal differentiation. 39 FBXL7 has been previously associated with several traits including the metabolic syndrome 40 and other vascular risk factors. Although never associated with LOAD at the genome-wide significant level, one SNP (rs11748700) within the FBXL7 gene, was among the top hits in later meta-analysis showed a combined P = 2.6E-06.…”

Section: Discussionmentioning

confidence: 99%

F‐box/ LRR ‐repeat protein 7 is genetically associated with Alzheimer's disease

Tosto

Vardarajan

et al. 2015

Ann Clin Transl Neurol

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ObjectiveIn the context of late-onset Alzheimer’s disease (LOAD) over 20 genes have been identified but, aside APOE, all show small effect sizes, leaving a large part of the genetic component unexplained. Admixed populations, such as Caribbean Hispanics, can provide a valuable contribution because of their unique genetic profile and higher incidence of the disease. We aimed to identify novel loci associated with LOAD.MethodsAbout 4514 unrelated Caribbean Hispanics (2451 cases and 2063 controls) were selected for genome-wide association analysis. Significant loci were further tested in the expanded cohort that also included related family members (n = 5300). Two AD-like transgenic mice models (J20 and rTg4510) were used to study gene expression. Independent data sets of non-Hispanic Whites and African Americans were used to further validate findings, along with publicly available brain expression data sets.ResultsA novel locus, rs75002042 in FBXL7 (5p15.1), was found genome-wide significant in the case–control cohort (odd ratio [OR] = 0.61, P = 6.19E-09) and confirmed in the related members cohorts (OR = 0.63, P = 4.7E-08). Fbxl7 protein was overexpressed in both AD-like transgenic mice compared to wild-type littermates. Publicly available microarray studies also showed significant overexpression of Fbxl7 in LOAD brains compared to nondemented controls. single-nucleotide polymorphism (SNP) rs75002042 was in complete linkage disequilibrium with other variants in two independent non-Hispanic White and African American data sets (0.0005 < P < 0.02) used for replication.InterpretationFBXL7, encodes a subcellular protein involved in phosphorylation-dependent ubiquitination processes and displays proapoptotic activity. F-box proteins also modulate inflammation and innate immunity, which may be important in LOAD pathogenesis. Further investigations are needed to validate and understand its role in this and other populations.

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APP intracellular domain acts as a transcriptional regulator of miR-663 suppressing neuronal differentiation

Cited by 50 publications

References 62 publications

Indirect Down-regulation of Tumor-suppressivelet-7Family MicroRNAs byLMO1in Neuroblastoma

Indirect Down-regulation of Tumor-suppressivelet-7Family MicroRNAs byLMO1in Neuroblastoma

Sexual Dimorphism and Aging in the Human Hyppocampus: Identification, Validation, and Impact of Differentially Expressed Genes by Factorial Microarray and Network Analysis

F‐box/ LRR ‐repeat protein 7 is genetically associated with Alzheimer's disease

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