Time-dependent differential expression of long non-coding RNAs following peripheral nerve injury

Abstract

Abstract. Long non-coding RNAs (lncRNAs) are widely accepted as key players in various biological processes. However, the roles of lncRNA in peripheral nerve regeneration remain completely unknown. Thus, in this study, we performed microarray analysis to measure lncRNA expression in the distal segment of the sciatic nerve at 0, 3, 7 and 14 days following injury. We identified 5,354 lncRNAs that were differentially expressed: 3,788 lncRNAs were differentially expressed between days 0 and 3; 3,314 lncRNAs were differentially expressed between days 0 and 7; and 2,400 lncRNAs were differentially expressed between days 0 and 14. The results of RT-qPCR of two dysregulated lncRNAs were consistent with those of microarray analysis. Bioinformatics approaches, including lncRNA classification, gene ontology (GO) analysis and target prediction, were utilized to investigate the functions of these dysregulated lncRNAs in peripheral nerve damage. Importantly, we predicted that several lncRNA-mRNA pairs may participate in biological processes related to peripheral nerve injury. RT-qPCR was performed for the preliminary verification of three lncRNA-mRNA pairs. The overexpression of NONMMUG014387 promoted the proliferation of mouse Schwann cells. Thus, the findings of our study may enhance our knowledge of the role of lncRNAs in nerve injury.

Non-coding RNAs in neuropathic pain

“…lncRNA tissue expression in animal models lncRNAs and circRNAs are differentially expressed in animal pain models in sciatic nerve, DRG and spinal cord [180][181][182][183][184][185]. Most of these studies combine lncRNA and mRNA expression analyses including complex bioinformatics to generate networks of potential functional interactions [180,186,187]; however, only few have been explored using a more mechanistic approach ( Table 5).…”

“…is time-dependent and varies between strains and species [182,183,185]. LncRNAs play important roles in neuropathic pain processes not only in neurons, but also in non-neuronal cells, such as Schwann cells, satellite glial cells, macrophages and microglia [74,83,185,[188][189][190][191].…”

“…lncRNAs deregulated in the peripheral nerve Differential expression of lncRNAs and circRNAs in peripheral nerves in neuropathic pain models have not been addressed in detail. Deregulated lncRNAs are reported in the sciatic nerve after a sciatic nerve crush [185]. This model is used to explore nerve regeneration and numerous differentially expressed lncRNAs were associated with inflammatory and immune responses, which could possibly be relevant for neuropathic pain [185].…”

“…Deregulated lncRNAs are reported in the sciatic nerve after a sciatic nerve crush [185]. This model is used to explore nerve regeneration and numerous differentially expressed lncRNAs were associated with inflammatory and immune responses, which could possibly be relevant for neuropathic pain [185]. Particularly, NONMMUG014387 enhances the proliferation of cultured mouse Schwann cells, presumably via cis-upregulation of collagene triple helix repeat containing 1 (Cthrc1) [185], whereas the antisense to the Egr2 promoter ncRNA (Egr2-antisense-RNA) down-regulates Egr2 and promotes demyelination upon peripheral nerve injury by an epigenetic mechanism, in which a chromatin remodeling complex is assembled at the Egr2 promoter [199].…”

Microarray analysis of the expression profile of lncRNAs reveals the key role of lncRNA BC088327 as an agonist to heregulin‑1β‑induced cell proliferation in peripheral nerve injury

“…recently, multiple studies have suggested that the mechanism asso ciated with injuries to the peripheral nerves depends on the function of various non-coding rnas (13)(14)(15)(16). among which, long non-coding rnas (lncrnas) have been shown to be involved in various biological processes and disease pathologies (17).…”