Systemic functional enrichment and ceRNA network identification following peripheral nerve injury

Abstract

Peripheral nerve injury is a worldwide clinical issue that impacts patients’ quality of life and causes huge society and economic burden. Injured peripheral nerves are able to regenerate by themselves. However, for severe peripheral nerve injury, the regenerative abilities are very limited and the regenerative effects are very poor. A better understanding of the mechanisms following peripheral nerve injury will benefit its clinical treatment. In this study, we systematically explored the dynamic changes of mRNAs and long non-coding RNAs (lncRNAs) in the injured sciatic nerve segments after nerve crush, identified significantly involved Gene ontology (GO) terms and Kyoto Enrichment of Genes and Genomes (KEGG) pathways, and innovatively analyzed the correlation of differentially expressed mRNAs and lncRNAs. After the clustering of co-expressed mRNAs and lncRNAs, we performed functional analysis, selected GO term “negative regulation of cell proliferation”, and constructed a competing endogenous RNA (ceRNA) network of LIF and HMOX1 gene in this GO term. This study is the first to provide a systematic dissection of mRNA-microRNA (miRNA)-lncRNA ceRNA network following peripheral nerve injury and thus lays a foundation for further investigations of the regulating mechanisms of non-coding RNAs in peripheral nerve repair and regeneration.Electronic supplementary materialThe online version of this article (10.1186/s13041-018-0421-4) contains supplementary material, which is available to authorized users.

WITHDRAWN: Identification of Non-coding RNA Biomarkers in Stress-induced Depression via Comprehensive Analysis of Competing Endogenous RNA Network

“…Besides, circRNA HDAC9 /miR-138 / Sirt1 was involved in synaptic dysfunction [54]. CeRNA analysis may offer promising insight into the mechanism of neuronal injury [55,56]. However, the evaluation of circRNA mediated ceRNA in underlying effect of depression remains ambiguous.…”

Leukemia inhibitory factor regulates Schwann cell proliferation and migration and affects peripheral nerve regeneration

“…Our previous study has examined the mRNA abundance of LIF in the injured rat sciatic nerve segments and demonstrated that LIF mRNA expression is upregulated at 1 day, 4 days, and 7 days after peripheral nerve injury and gradually recovered to the normal level at 14 days after nerve injury 13 . Rat sciatic nerve segments were further subjected to immunostaining to determine the protein abundance of LIF after nerve injury.…”

“…Previously, we have screened differentially expressed genes in rat sciatic nerve segments after peripheral nerve injury, discovered enriched Gene Ontology (GO) terms, and found that LIF, a gene encoding leukemia inhibitory factor (LIF), is involved in the GO term “negative regulation of cell proliferation” 13 . LIF is a neurotrophic factor that supports the development and survival of neurons and rescues neuronal death after axotomy 14 – 17 .…”

miR-328a-3p stimulates endothelial cell migration and angiogenesis

“…The sequences of miR-328a-3p were highly conserved in different species, including human (H. Sapiens) and rats (R. Norvegicus). Considering that we have obtained the transcriptome pro les and identi ed ceRNA networks of rats after peripheral nerve injury (33), here, we determined lncRNA-miR-328a-3p-mRNA interactions, constructed a miR-328a-3p-centered ceRNA network, and explored the temporal expression patterns of miR-328a-3p-associated lncRNAs and mRNAs in the injured sciatic nerves of rats. Following peripheral nerve injury, the expression levels of miR-328a-3p rst decreased, reaching a valley level at 4 days after nerve injury, and then gradually recovered to the uninjured level at 14 days (12).…”