MicroRNAs expressed in neuronal differentiation and their associated pathways: Systematic review and bioinformatics analysis

Giorgi, Roberta; Ferrúa, Camila Perelló; Amaral, Cainá Corrêa do; Garcia, Tiago Fernandez; Souza, Karoline Brizola de; Nedel, Fernanda

doi:10.1016/j.brainresbull.2020.01.009

Cited by 26 publications

(12 citation statements)

References 66 publications

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“…MiRNAs represent the key “fine‐tuners” of gene expression during the differentiation of hPSCs. It has been previously shown that manipulation with single miRNA or the whole miRNA cluster/family may have a significant impact on differentiation outcomes of pluripotent stem cells 16‐19 . Here, we show that the miR‐183/96/182 cluster regulates PAX6 expression in differentiating hPSCs into retinal organoids.…”

Section: Discussionmentioning

confidence: 52%

miR-183/96/182 cluster is an important morphogenetic factor targeting PAX6 expression in differentiating human retinal organoids

et al. 2020

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MicroRNAs (miRNAs), a class of small, noncoding RNA molecules, represent important regulators of gene expression. Recent reports have implicated their role in the cell specification process acting as "fine-tuners" to ensure the precise gene expression at the specific stage of cell differentiation. Here, we used retinal organoids differentiated from human pluripotent stem cells (hPSCs) as a model to closely investigate the role of a sensory organ-specific and evolutionary conserved miR-183/96/182 cluster. Using a miRNA tough decoy approach, we inhibited the miR-183/96/182 cluster in hPSCs. Inhibition of the miRNA cluster resulted in an increased expansion of neuroepithelium leading to abnormal "bulged" neural retina in organoids, associated with upregulation of neural-specific and retinal-specific genes. Importantly, we identified PAX6, a well-known essential gene in neuroectoderm specification, as a target of the miR-183/96/182 cluster members. Taken together, the miR-183/96/182 cluster not only represents an important regulator of PAX6 expression, but it also plays a crucial role in retinal tissue morphogenesis.

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Section: Discussionmentioning

confidence: 52%

miR-183/96/182 cluster is an important morphogenetic factor targeting PAX6 expression in differentiating human retinal organoids

et al. 2020

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“…The dramatic transcriptional alterations in multiple mRNAs related to specific myelination and cell differentiation pathways in NexKO mice [ 56 ] have led us to explore whether there are master regulators that mediate these changes. The myriad of data supporting the involvement of microRNAs (miRNAs or miRs) in the development of the nervous system [ 60 , 61 , 62 , 63 , 64 , 65 , 66 ] encouraged us to explore miRNAs in the context of the neurodevelopmental deficits found in NexKO mice compared to controls. miRNAs are small (~22 nucleotides), endogenous, non-coding RNA molecules that downregulate mRNA expression post-transcriptionally, thus leading to a reduced expression of their protein products [ 60 , 67 ].…”

Section: Introductionmentioning

confidence: 99%

“…One miRNA can target hundreds of mRNAs, and in this way influence extensive cellular pathways, acting as a “master regulator” of gene expression [ 62 , 68 , 72 ]. The largest variety of expressed miRNAs exists in the central nervous system (CNS), thus implicating their importance in CNS regulation [ 60 , 61 , 62 , 63 , 64 , 73 ]. Moreover, some miRNAs share the same seed sequence, thus creating a cluster of miRNAs that commonly target mRNAs belonging to the same biological pathway or molecular function [ 60 , 67 ], wherein different miRNAs of the same cluster can be differentially expressed, depending on the temporal and spatial context, and can thus fine-tune mRNA expression to yield the optimal protein levels for the specific cellular context [ 60 , 67 ].…”

Section: Introductionmentioning

confidence: 99%

Altered White Matter and microRNA Expression in a Murine Model Related to Williams Syndrome Suggests That miR-34b/c Affects Brain Development via Ptpru and Dcx Modulation

Grad

Nir

Levy

et al. 2022

Cells

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Williams syndrome (WS) is a multisystem neurodevelopmental disorder caused by a de novo hemizygous deletion of ~26 genes from chromosome 7q11.23, among them the general transcription factor II-I (GTF2I). By studying a novel murine model for the hypersociability phenotype associated with WS, we previously revealed surprising aberrations in myelination and cell differentiation properties in the cortices of mutant mice compared to controls. These mutant mice had selective deletion of Gtf2i in the excitatory neurons of the forebrain. Here, we applied diffusion magnetic resonance imaging and fiber tracking, which showed a reduction in the number of streamlines in limbic outputs such as the fimbria/fornix fibers and the stria terminalis, as well as the corpus callosum of these mutant mice compared to controls. Furthermore, we utilized next-generation sequencing (NGS) analysis of cortical small RNAs’ expression (RNA-Seq) levels to identify altered expression of microRNAs (miRNAs), including two from the miR-34 cluster, known to be involved in prominent processes in the developing nervous system. Luciferase reporter assay confirmed the direct binding of miR-34c-5p to the 3’UTR of PTPRU—a gene involved in neural development that was elevated in the cortices of mutant mice relative to controls. Moreover, we found an age-dependent variation in the expression levels of doublecortin (Dcx)—a verified miR-34 target. Thus, we demonstrate the substantial effect a single gene deletion can exert on miRNA regulation and brain structure, and advance our understanding and, hopefully, treatment of WS.

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“…In comparison, miR-320b is also expressed in the brain and has been implicated in neuronal differentiation 16 , 17 , regulation of inflammatory processes via the nucleotide-binding oligomerization domain 18 , and regulation of endoplasmic reticulum stress 19 . miR-320b is robustly increased in anterior cingulate cortex and habenula of individuals with MDD 20 , regions of the brain thought to be important for pain affect and processing 21 , 22 .…”

Section: Introductionmentioning

confidence: 99%

Neuronally-enriched exosomal microRNA-27b mediates acute effects of ibuprofen on reward-related brain activity in healthy adults: a randomized, placebo-controlled, double-blind trial

Burrows

Figueroa-Hall

Kuplicki

et al. 2022

Sci Rep

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This double-blind, randomized, within-subjects design evaluated whether acute administration of an anti-inflammatory drug modulates neuron-specific, inflammation-modulating microRNAs linked to macroscopic changes in reward processing. Twenty healthy subjects (10 females, 10 males) underwent a functional magnetic resonance imaging scan while performing a monetary incentive delay (MID) task and provided blood samples after administration of placebo, 200 mg, or 600 mg of ibuprofen. Neuronally-enriched exosomal microRNAs were extracted from serum and sequenced. Results showed that: (1) 600 mg of ibuprofen exhibited higher miR-27b-3p, miR-320b, miR-23b and miR-203a-3p expression than placebo; (2) higher mir-27b-3p was associated with lower insula activation during MID loss anticipation; and (3) there was an inverse relationship between miR-27b-3p and MID gain anticipation in bilateral putamen during placebo, a pattern attenuated by both 200 mg and 600 mg of ibuprofen. These findings are consistent with the hypothesis that miR-27b could be an important messaging molecule that is associated with regulating the processing of positive or negative valenced information.

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MicroRNAs expressed in neuronal differentiation and their associated pathways: Systematic review and bioinformatics analysis

Cited by 26 publications

References 66 publications

miR-183/96/182 cluster is an important morphogenetic factor targeting PAX6 expression in differentiating human retinal organoids

miR-183/96/182 cluster is an important morphogenetic factor targeting PAX6 expression in differentiating human retinal organoids

Altered White Matter and microRNA Expression in a Murine Model Related to Williams Syndrome Suggests That miR-34b/c Affects Brain Development via Ptpru and Dcx Modulation

Neuronally-enriched exosomal microRNA-27b mediates acute effects of ibuprofen on reward-related brain activity in healthy adults: a randomized, placebo-controlled, double-blind trial

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