hsa-let-7c miRNA Regulates Synaptic and Neuronal Function in Human Neurons

McGowan, Heather; Mirabella, Vincent R.; Hamod, Aula; Karakhanyan, Aziz; Mlynaryk, Nicole; Moore, Jennifer C.; Tischfield, Jay A.; Hart, Ronald P.; Pang, Zhiping P.

doi:10.3389/fnsyn.2018.00019

Cited by 27 publications

(35 citation statements)

References 52 publications

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“…In addition, a number of miRNAs have been shown to be involved in synapses and may participate in the regulation of synaptic development, as well as functional regulation (42). A previous study reported that miR-134-5p is involved in the development and morphological changes of synapses (43). miR-134 is found in neurons and dendrites of primary cultured neurons, where it regulates the development of the dendritic spine by targeting LimK1 mRNA, which can be inhibited by BDNF (18).…”

Section: Discussionmentioning

confidence: 99%

miR‑134‑5p/Foxp2/Syn1 is involved in cognitive impairment in an early vascular dementia rat model

Liu

Zhang

et al. 2019

Int J Mol Med

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Forkhead box P2 (Foxp2) is a transcription factor involved in vocal learning. However, the number of previous studies that have investigated the role of Foxp2 in early vascular dementia (Vd) is limited. The aim of the present study was to determine whether microRNA (miR)-134-5p/Foxp2 contributes to cognitive impairment in a chronic ischemia-induced early Vd model. miR-134-5p was found to be significantly increased in the cortex in a rat Vd model. Intracerebroventricular injection of miR-134-5p antagomir into Vd rats prevented the loss of synaptic proteins and the development of cognitive impairment phenotypes. Histopathological analysis revealed that miR-134-5p aggravated cognitive impairment in Vd rats through damage to cortical neurons and loss of synaptic proteins. Bioinformatics analysis predicted that miR-134-5p targets Foxp2 mRNA. dual luciferase analysis and western blotting supported the prediction that miR-134-5p targets Foxp2. Furthermore, the silencing of Foxp2 significantly inhibited the effect of miR-134-5p on synaptic protein loss. chromatin immunoprecipitation-quantitative polymerase chain reaction analysis indicated that Foxp2 binds to the synapsin I (Syn1) promoter at-400/-600 bp upstream of the transcription start site. In conclusion, the miR-134-5p/Foxp2/Syn1 axis was found to contribute to cognitive impairment in a chronic ischemia-induced early Vd model, which may enable the development of new therapeutic strategies for the prevention and treatment of Vd.

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Section: Discussionmentioning

confidence: 99%

miR‑134‑5p/Foxp2/Syn1 is involved in cognitive impairment in an early vascular dementia rat model

Liu

Zhang

et al. 2019

Int J Mol Med

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“…miR-let-7e expression was strongly correlated with the development of EAE symptoms (31). In addition, miRNAs of the let-7 family have been described several times in various studies in the context of neurogenesis and axonal guidance (58,60,74,94,101). MiRlet-7 was described in conjunction with neurodegenerative processes (45,80).…”

Section: Potential Targets Of Dysregulated Mirnas In Gm-ms-lesionsmentioning

confidence: 99%

“…Interestingly, the occurrence in neurons has been described for the miRNAs miR-330 (14) and miR574 (49) and some miRNAs of the let-7 family (58,60,74,94,101).…”

Section: Six Mirnas Show Stronger Upregulation In Gm Lesions Than In mentioning

confidence: 99%

MicroRNA profiles of MS gray matter lesions identify modulators of the synaptic protein synaptotagmin‐7

et al. 2019

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We established microRNA (miRNA) profiles in gray and white matter multiple sclerosis (MS) lesions and identified seven miRNAs which were significantly more upregulated in the gray matter lesions. Five of those seven miRNAs, miR-330-3p, miR-4286, miR-4488, let-7e-5p, miR-432-5p shared the common target synaptotagmin7 (Syt7). Immunohistochemistry and transcript analyses using nanostring technology revealed a maldistribution of Syt7, with Syt7 accumulation in neuronal soma and decreased expression in axonal structures. This maldistribution could be at least partially explained by an axonal Syt7 transport disturbance. Since Syt7 is a synapseassociated molecule, this maldistribution could result in impairment of neuronal functions in MS patients. Thus, our results lead to the hypothesis that the overexpression of these five miRNAs in gray matter lesions is a cellular mechanism to reduce further endogenous neuronal Syt7 production. Therefore, miRNAs seem to play an important role as modulators of neuronal structures in MS.

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“…The copyright holder for this preprint this version posted October 27, 2020. ; https://doi.org/10.1101/2020.10.24.20218677 doi: medRxiv preprint neurodegeneration (15), and neurodevelopmental disorders (10). while DS and AD have been found to have robust associations to dyslipidemias, particularly low HDL-Col concentration, common conditions in DS patients (16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Profiling of circulating chromosome 21-encoded microRNAs, miR-155 and Let-7c, in Down Syndrome People

Perez-Villareal

Aviña-Padilla

Lopez

et al. 2020

Preprint

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Down syndrome (DS), or Trisomy 21 (Ts21), is the most common chromosomal survival aneuploidy. Nevertheless, people with DS have compromised health, and the increase in their life expectancy further heightens the risk of developing chronic degenerative diseases such as obesity, dyslipidemias and diabetes mellitus associated with higher morbidity, and mortality for cardiovascular disease from an early age. DS is also accompanied by a higher risk of neurodegeneration. The extra genetic material that characterizes DS causes an imbalance in the genetic dosage, including overexpression of miR-155 and Let-7c miRNAs, both associated with cognitive impairment and dementia in adults. The dynamics of expression of their putative target genes in the early stages of the development of DS and their clinical associations, however, remain to be ascertained. This study aimed to evaluate the relative expression of miR-155 and Let-7c in young and adult individuals with DS and its possible association with biochemical indicators of lipid metabolism. The anthropometric, clinical, biochemical, and gene expression features of miR-155 and Let-7c were analyzed in a population of 52 control and 50 DS subjects divided into groups of 20 years of age or younger and 21 years or older. Expression changes for miR-155 were not significant. Nevertheless, a negative correlation for HDL-Cholesterol concentrations and miR-155 expression was identified. Notably, Let-7c was overexpressed in DS from young and old ages. Overall, our results suggest that Let-7c is related from early stages to cognitive impairment in DS, while a similar role of miR-155 in late stages could be mediated by alterations in lipid metabolism. Further studies with both miRNAs will shed light on their potential as therapeutic targets to prevent or delay cognitive impairment in DS.

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hsa-let-7c miRNA Regulates Synaptic and Neuronal Function in Human Neurons

Cited by 27 publications

References 52 publications

miR‑134‑5p/Foxp2/Syn1 is involved in cognitive impairment in an early vascular dementia rat model

miR‑134‑5p/Foxp2/Syn1 is involved in cognitive impairment in an early vascular dementia rat model

MicroRNA profiles of MS gray matter lesions identify modulators of the synaptic protein synaptotagmin‐7

Profiling of circulating chromosome 21-encoded microRNAs, miR-155 and Let-7c, in Down Syndrome People

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