XIST/miR-544 axis induces neuropathic pain by activating STAT3 in a rat model.

An increasing number of studies have reported that lncRNAs are responsible for the development of neuropathic pain. In our current study, chronic constriction injury (CCI) rat models were established and we observed that lncRNA XIST was greatly increased. Knockdown of XIST can relieve pain characteristics including both mechanical and thermal hyperalgesia in CCI rats. Meanwhile, XIST down-regulation could inhibit neuro-inflammation by reducing expression of inflammatory cytokines including tumor necrosis factor (TNF)-α, IL-1β, and IL-6 and in CCI rats. By performing bioinformatics technology, miR-544 was predicted to have interactions with XIST and dual-luciferase reporter assays validated the correlation between them. A negative correlation between miR-544 and XIST was observed by carrying out XIST loss or gain of function tests. miR-544 markedly alleviated neuropathic pain development in CCI rats via targeting inflammatory cytokines, which was reversed by XIST over-expression. Moreover, STAT3 was manifested to be a target gene of miR-544 by bioinformatics predictions and it was activated in CCI rats. Over-expression of STAT3 was able to induce neuropathic pain and miR-544 inhibited this process in vivo. Furthermore, XIST increased STAT3 expression by sponging miR-544 in neuropathic pain development. To conclude, our present study indicated that XIST can contribute to neuropathic pain progression in rats through down-regulating miR-544 and up-regulating STAT3. Our results suggested that XIST/miR-544/STAT3 axis can serve as a novel therapeutic target in neuropathic pain development.