Long non-coding RNA CCAT1 modulates neuropathic pain progression through sponging miR-155

Abstract

Neuropathic pain is caused by dysfunction or primary injury of the somatosensory nervous system. Long noncoding RNAs (lncRNAs) play important roles in the development of neuropathic pain. However, the effects of lncRNA colon cancer associated transcript-1 (CCAT1) in neuropathic pain have not been reported. The model of bilateral sciatic nerve chronic constriction injuries (bCCI) is regarded as long-lasting mechanical hypersensitivity and cold allodynia, which is the representative symptom in the human subjects suffering from the neuropathic pain. In this study, we found that CCAT1 expression was decreased in the spinal dorsal horn, dorsal root ganglion (DRG), hippocampus, and anterior cingulate cortex (ACC) of rats with bCCI. The rats of bCCI presented the cold allodynia after the 14th day of postoperation. We furtherly showed that lncRNA CCAT1 decreased miR-155 expression and enhanced Serum and glucocorticoid regulated protein kinase 3 (SGK3) expression in the NGF-differentiated PC12 cell. We found that miR-155 expression was increased in the spinal dorsal horn, DRG, hippocampus, and ACC of rats with bCCI injuries. However, SGK3 expression was downregulated in the spinal dorsal horn, DRG, hippocampus, and ACC of rats with bCCI injuries. Moreover, lncRNA CCAT1 overexpression could alleviate the pain thresholds and inhibited expression of SGK3 could rescue this effect. In conclusion, these results suggested the crucial roles of CCAT1 and SGK3 in the neuropathic pain.

MiR‐28‐5p relieves neuropathic pain by targeting Zeb1 in CCI rat models

“…miR‐30b can regulate the sodium channel Nav1.7 in rats with neuropathic pain . In addition, lncRNA CCAT1 can regulate neuropathic pain progression by targeting miR‐155 . LncRNA Kcna2 antisense RNA promotes neuropathic pain by inhibiting Kcna2 .…”

Current Evidence on the Role of Epigenetic Mechanisms in Migraine: The Way Forward to Precision Medicine

“…Recent evidence indicates that lncRNAs are upregulated or downregulated in some neuropathic pain models. For example, the expression of lncRNA colon cancer-associated transcript-1 (CCAT1) in a neuropathic pain model of bilateral sciatic nerve chronic constriction injuries (bCCI) has been found to be decreased [93]. In this study, lncRNA CCAT1 overexpression was demonstrated to increase pain threshold and reverse cold allodynia in rats.…”

Functional roles of lncRNAs and its potential mechanisms in neuropathic pain

“…Yu et al [60] found that silencing of FKBP51 alleviated the mechanical pain threshold and inhibited DRG inflammatory factors and pain mediators through the NF-κB signaling pathway. Dou et al [61] revealed that overexpression of CCAT1 partially alleviated the pain threshold by acting as a sponge for miR-155 through targeting SGK3. SGK3 is an important inflammatory signaling protein that plays a key role in signaling pathways and cellular phosphorylation cascade [62].…”

“…For instance, studies have shown that the MAPK and NF-κB signaling pathways regulated by lncRNAs may be responsible for the majority of inflammatory mediator-signaling actions within nociceptive neurons [54,60,79,80]. The ERK pathway, as a branch of the MAPK signaling pathway, is another main pathway that indicates a relationship between lncRNAs and NP [61,80]. In addition, Zhang et al [81] used Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis and pathway network analysis to disclose differentially expressed genes and activated signaling pathways in association with SCI-induced NP and found that 209 pathways changed significantly; among them, the most significantly activated one is the MAPK signaling pathway.…”