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 ORCID: https://orcid.org/0000-0002-0217-3322, Signorino, Elena, Berto, Gaia Elena, Pourshayesteh, Soraya, Singh, Archana, Di Cunto, Ferdinando, Dalmay, Tamas ORCID: https://orcid.org/0000-0003-1492-5429 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
UEA Research Groups:	Faculty of Science > Research Groups > Plant Sciences Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	06 Mar 2021 00:57
Last Modified:	19 Oct 2023 02:55
URI:	https://ueaeprints.uea.ac.uk/id/eprint/79389
DOI:	10.3389/fmolb.2021.618869

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