AUTHOR=Yin Gang , Peng Ying , Lin Yaofa , Wang Peilin , Li Zhuoxuan , Wang Renyuan , Lin Haodong 

TITLE=Long Non-coding RNA MSTRG.24008.1 Regulates the Regeneration of the Sciatic Nerve via the miR-331-3p–NLRP3/MAL Axis

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.641603

DOI=10.3389/fcell.2021.641603

ISSN=2296-634X

ABSTRACT=<p>Peripheral nerve injury (PNI) is a common clinical problem, which can cause severe disability and dramatically affect a patient’s quality of life. Neural regeneration after PNI is a complex biological process that involves a variety of signaling pathways and genes. Emerging studies demonstrated that long non-coding RNAs (lncRNAs) were abnormally expressed after PNI and played pivotal roles in peripheral nerve regeneration. Based on the rat sciatic nerve injury model, we found that the expression levels of several lncRNAs were increased significantly in the sciatic nerve after injury. Software prediction prompted us to focus on one up-regulated lncRNA, <italic>MSTRG.24008.1</italic>. Dual-luciferase reporter assay, RNA pull-down assay and RNA interference approach verified that <italic>MSTRG.24008.1</italic> regulated neuroregeneration via the miR-331-3p/nucleotide-binding oligomerization domain-like pyrin domain containing 3 (NLRP3)/myelin and lymphocyte protein (MAL) axis <italic>in vitro</italic>. Subsequently, we performed gastrocnemius muscle gravity and sciatic functional index experiments to evaluate the recovery of injured sciatic nerves after <italic>MSTRG.24008.1</italic> siRNA interference <italic>in vivo</italic>. In conclusion, knockdown of <italic>MSTRG.24008.1</italic> promotes the regeneration of the sciatic nerve via the miR-331-3p/NLRP3/MAL axis, which may provide a new strategy to evaluate and repair injured peripheral nerves clinically.</p>