Network analysis of microRNAs, transcription factors, and target genes involved in axon regeneration

Su, Li-ning; Song, Xiu–Peng; Zhou, Xue; Zheng, Chenqing; Yin, Haifeng; H, Wei

doi:10.1631/jzus.b1700179

Cited by 30 publications

(31 citation statements)

References 35 publications

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“…In addition to miR-323a-3p, we also identified overexpression of miR-204-5p, miR-320b, and miR-331-3p in the brains of depressed individuals. MiR-204 appears to have numerous important functions in the nervous system, including axon regeneration 59 and hippocampal ageing 60 , stem cell differentiation 61 , and notable targets include EPH receptor B2 (EPHB2) 60 , tropomyosin related kinase type B (TrkB) 62 , and ERBB3 63 . Additionally, this miRNA has been associated with schizophrenia 64 , and is responsive to social enrichment in a rat model of fetal alcohol disorder 65 .…”

Section: Relationship Between Mir-323-3p and Erbb4 In Micementioning

confidence: 99%

miR-323a regulates ERBB4 and is involved in depression

et al. 2020

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Major depressive disorder (MDD) is a complex and debilitating illness whose etiology remains unclear. Small RNA molecules, such as micro RNAs (miRNAs) have been implicated in MDD, where they display differential expression in the brain and the periphery. In this study, we quantified miRNA expression by small RNA sequencing in the anterior cingulate cortex and habenula of individuals with MDD and psychiatrically-healthy controls. Thirty-two miRNAs showed significantly correlated expression between the two regions (False Discovery Rate < 0.05), of which four, miR-204-5p, miR-320b, miR-323a-3p, and miR-331-3p, displayed upregulated expression in MDD. We assessed the expression of predicted target genes of differentially expressed miRNAs in the brain, and found that the expression of erb-b2 receptor tyrosine kinase 4 (ERBB4), a gene encoding a neuregulin receptor, was downregulated in both regions, and was influenced by miR-323a-3p in vitro. Finally, we assessed the effects of manipulating miRNA expression in the mouse ACC on anxiety-and depressive-like behaviors. Mice in which miR-323-3p was overexpressed or knocked-down displayed increased and decreased emotionality, respectively. Additionally, these mice displayed significantly downregulated and upregulated expression of Erbb4, respectively. Overall, our findings indicate the importance of brain miRNAs in the pathology of MDD, and emphasize the involvement of miR-323a-3p and ERBB4 in this phenotype. Future studies further characterizing miR-323a-3p and neuregulin signaling in depression are warranted.

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Section: Relationship Between Mir-323-3p and Erbb4 In Micementioning

confidence: 99%

miR-323a regulates ERBB4 and is involved in depression

et al. 2020

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“…In particular, HSV infection was the most significantly enriched pathway in FUS-ALS patients associated with zinc-finger proteins as the major key involved genes. Notably, the majority of the enriched pathways in ALS patients have already been associated with ALS pathogenesis, such as immune/inflammatory response, T cell activation, viral infection and apoptosis [ 28 , 29 , 30 , 31 , 32 , 33 ]. The top significant pathways are given in Figure 2 B and the full list of all KEGG pathways is given in Table S3 .…”

Section: Resultsmentioning

confidence: 99%

Genome Wide Analysis Points towards Subtype-Specific Diseases in Different Genetic Forms of Amyotrophic Lateral Sclerosis

Dash

Naumann

Sterneckert

et al. 2020

IJMS

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Amyotropic lateral sclerosis (ALS) is a lethally progressive and irreversible neurodegenerative disease marked by apparent death of motor neurons present in the spinal cord, brain stem and motor cortex. While more and more gene mutants being established for genetic ALS, the vast majority suffer from sporadic ALS (>90%). It has been challenging, thus, to model sporadic ALS which is one reason why the underlying pathophysiology remains elusive and has stalled the development of therapeutic strategies of this progressive motor neuron disease. To further unravel these pathological signaling pathways, human induced pluripotent stem cell (hiPSCs)-derived motor neurons (MNs) from FUS- and SOD1 ALS patients and healthy controls were systematically compared to independent published datasets. Here through this study we created a gene profile of ALS by analyzing the DEGs, the Kyoto encyclopedia of Genes and Genomes (KEGG) pathways, the interactome and the transcription factor profiles (TF) that would identify altered molecular/functional signatures and their interactions at both transcriptional (mRNAs) and translational levels (hub proteins and TFs). Our findings suggest that FUS and SOD1 may develop from dysregulation in several unique pathways and herpes simplex virus (HSV) infection was among the topmost predominant cellular pathways connected to FUS and not to SOD1. In contrast, SOD1 is mainly characterized by alterations in the metabolic pathways and alterations in the neuroactive-ligand–receptor interactions. This suggests that different genetic ALS forms are singular diseases rather than part of a common spectrum. This is important for patient stratification clearly pointing towards the need for individualized medicine approaches in ALS.

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“…It also regulates liver glucose homeostasis by modulating the expression of gluconeogenic genes (Inoue et al, 2004). A gene co-regulatory network analysis identified RAB11FIP2 as a differentially expressed gene in axon regeneration, suggesting its possible role in atrophy (Su et al, 2018). Correspondingly, a growing body of evidence supports the gene-imaging interactions we found in longitudinal alterations in atrophy.…”

Section: Discussionmentioning

confidence: 99%

Integrated Transcriptomic and Neuroimaging Brain Model Decodes Biological Mechanisms in Aging and Alzheimer’s Disease

Adewale

Khan

Carbonell

et al. 2021

Preprint

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Both healthy aging and Alzheimer disease (AD) are characterized by concurrent alterations in several biological factors. However, generative brain models of aging and AD are limited in incorporating the measures of these biological factors at different spatial resolutions. Here, we propose a personalized bottom-up spatiotemporal brain model which accounts for the direct interplay between hundreds of RNA transcripts and multiple macroscopic neuroimaging modalities (PET, MRI). In normal elderly and AD participants, the model identifies top genes modulating tau and amyloid-β burdens, vascular flow, glucose metabolism, functional activity, and atrophy to drive cognitive decline. The results also revealed that AD and healthy aging share specific biological mechanisms, even though AD is a separate entity with considerably more altered pathways. Overall, this personalized model offers novel insights into the multiscale alterations in the elderly brain, with important implications for identifying effective genetic targets for extending healthy aging and treating AD progression.

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Network analysis of microRNAs, transcription factors, and target genes involved in axon regeneration

Cited by 30 publications

References 35 publications

miR-323a regulates ERBB4 and is involved in depression

miR-323a regulates ERBB4 and is involved in depression

Genome Wide Analysis Points towards Subtype-Specific Diseases in Different Genetic Forms of Amyotrophic Lateral Sclerosis

Integrated Transcriptomic and Neuroimaging Brain Model Decodes Biological Mechanisms in Aging and Alzheimer’s Disease

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