miR-7b-3p exerts a dual role after spinal cord injury, by supporting plasticity and neuroprotection at cortical level

Ghibaudi, Matilde, Boido, Marina, Green, Darrell, Signorino, Elena, Berto, Gaia E., Pourshayesteh, Soraya, Singh, Archana, Di Cunto, Ferdinando, Dalmay, Tamas and Vercelli, Alessandro (2021) miR-7b-3p exerts a dual role after spinal cord injury, by supporting plasticity and neuroprotection at cortical level. Frontiers in Molecular Biosciences, 8. ISSN 2296-889X

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Abstract

Spinal cord injury (SCI) affects 6 million people worldwide with no available treatment. Despite research advances, the inherent poor regeneration potential of the central nervous system remains a major hurdle. Small RNAs (sRNAs) 19–33 nucleotides in length are a set of non-coding RNA molecules that regulate gene expression and have emerged as key players in regulating cellular events occurring after SCI. Here we profiled a class of sRNA known as microRNAs (miRNAs) following SCI in the cortex where the cell bodies of corticospinal motor neurons are located. We identified miR-7b-3p as a candidate target given its significant upregulation after SCI in vivo and we screened by miRWalk PTM the genes predicted to be targets of miR-7b-3p (among which we identified Wipf2, a gene regulating neurite extension). Moreover, 16 genes, involved in neural regeneration and potential miR-7b-3p targets, were found to be downregulated in the cortex following SCI. We also analysed miR-7b-3p function during cortical neuron development in vitro: we observed that the overexpression of miR-7b-3p was important (1) to maintain neurons in a more immature and, likely, plastic neuronal developmental phase and (2) to contrast the apoptotic pathway; however, in normal conditions it did not affect the Wipf2 expression. On the contrary, the overexpression of miR-7b-3p upon in vitro oxidative stress condition (mimicking the SCI environment) significantly reduced the expression level of Wipf2, as observed in vivo, confirming it as a direct miR-7b-3p target. Overall, these data suggest a dual role of miR-7b-3p: (i) the induction of a more plastic neuronal condition/phase, possibly at the expense of the axon growth, (ii) the neuroprotective role exerted through the inhibition of the apoptotic cascade. Increasing the miR-7b-3p levels in case of SCI could reactivate in adult neurons silenced developmental programmes, supporting at the same time the survival of the axotomised neurons.

Item Type: Article
Uncontrolled Keywords: wipf2,axon regeneration,mirnas,neuronal development,spinal cord injury,sprouting,biochemistry,molecular biology,biochemistry, genetics and molecular biology (miscellaneous) ,/dk/atira/pure/subjectarea/asjc/1300/1303
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Biological Sciences
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 06 Mar 2021 00:57
Last Modified: 11 May 2021 00:12
URI: https://ueaeprints.uea.ac.uk/id/eprint/79389
DOI: 10.3389/fmolb.2021.618869

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