Inhibition of lncRNA DILC attenuates neuropathic pain via the SOCS3/JAK2/STAT3 pathway.
Long noncoding RNAs (lncRNAs) have been involved in the development of multiple pathological processes including neuropathic pain. The aim of the present study is to investigate the role of lncRNA down-regulated in liver cancer stem cells (DILC) in the progression of neuropathic pain and its underlying mechanism. Neuropathic pain rat model was established with the bilateral chronic constriction injury (bCCI) method. The results from quantitative PCR analysis in the spinal cord showed that DILC was significantly up-regulated in rats with bCCI compared with the sham group. DILC down-regulation mediated by intrathecal administration of DILC siRNA significantly increased the mechanical shrinkage threshold (MWT) and paw withdrawal threshold latency (PWTL), decreased the positive frequency for nerve sensitivity to cold and suppressed the expression of inflammatory genes in bCCI rats. Down-regulation of DILC induced suppressor of cytokine signaling (SOCS3) expression and inhibited the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) in spinal cord tissues. Western blotting showed that down-regulation of DILC by DILC siRNA transfection induced SOCS3 expression and inhibited the expression of p-Janus kinase 2 (p-JAK2) and p-STAT3 and their downstream genes in primary microglia. Furthermore, down-regulation of DILC increased the viability of primary microglia, suppressed apoptosis, and inhibited the production of interleukin (IL)-6 and IL-1β in microglia. In contrast, overexpression of DILC showed the opposite functions to those of DILC knockdown. In conclusion, silence of lncRNA DILC attenuates neuropathic pain via SOCS3-induced suppression of the JAK2/STAT3 pathway.
['Liu|Yujie|Y|', 'Feng|Lu|L|', 'Ren|Shichao|S|', 'Zhang|Yingxiu|Y|', 'Xue|Jing|J|']
D000818:Animals D017209:Apoptosis D002478:Cells, Cultured D004195:Disease Models, Animal D005786:Gene Expression Regulation D018836:Inflammation Mediators D053614:Janus Kinase 2 D008297:Male D017628:Microglia D009437:Neuralgia D017288:Pain Threshold D010766:Phosphorylation D062085:RNA, Long Noncoding D034741:RNA, Small Interfering D000067492:RNAi Therapeutics D017207:Rats, Sprague-Dawley D050796:STAT3 Transcription Factor D015398:Signal Transduction D013116:Spinal Cord D000071223:Suppressor of Cytokine Signaling 3 Protein
lncRNA DILC neuropathic pain SOCS3 the JAK2/STAT3 pathway inflammation