miR-7b-3p Exerts a Dual Role After Spinal Cord Injury, by Supporting Plasticity and Neuroprotection at Cortical Level

Frontiers in  Molecular Biosciences , 31 March 2021

miR-7b-3p Exerts a Dual Role After Spinal Cord Injury, by Supporting Plasticity and Neuroprotection at Cortical Level

Ghibaudi M ^1,2,* , Boido M ¹ , Green D ³ , Signorino E ¹ , Berto GE ¹ , Pourshayesteh S ¹ , Singh A ^4† , Di Cunto F ¹ , Dalmay T ^4† , Vercelli A ¹

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.

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Deregulated miRNAs after spinal cord injury (SCI), represented as “heat map”, in 4 experimental groups (P15 12 ore, P15 3 giorni, P90 12 ore, P90 3 giorni).B) miR-7b-3p upregulation was confirmed in all SCI groups by real time PCR.

¹  Department of Neuroscience “Rita Levi Montalcini,” Neuroscience Institute Cavalieri Ottolenghi, University of Turin, Orbassano, Italy
²  Polymers and Biomaterials, Italian Institute of Technology, Genova, Italy
³  Norwich Medical School, University of East Anglia, Norwich, United Kingdom
⁴  School of Biological Sciences, University of East Anglia, Norwich, United Kingdom

Second article:

Francesca Garello, ^1,†  Marina Boido, ^2,3,4,*†  Martina Miglietti, ³  Valeria Bitonto, ¹  Marco Zenzola, ¹  Miriam Filippi, ¹  Francesca Arena, ^1,5  Lorena Consolino, ¹  Matilde Ghibaudi, ^2,3  and Enzo Terreno ^1,*  (2021)  Imaging of Inflammation in Spinal Cord Injury: Novel Insights on the Usage of PFC-Based Contrast Agents .   Biomedicines