Suppression of the lncRNA TUG1 alleviates neuropathic pain in rats with chronic contractile injury via the miR-29b-3p/HMGB1 axis.

Abstract

The present research focused on the function of lncRNA taurine upregulated 1 (TUG1) in a rat neuropathic pain (NP) model constructed by chronic contractile injury (CCI). Construction of the NP rat model was performed by CCI surgery. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were applied to examine the NP behavior. RT-qPCR was established to explore the levels of TUG1, microRNA (miR)-29b-3p, and HMGB1. ELISA was carried out to evaluate the concentrations of interleukin (IL)-6, IL-1β, tumor necrosis factor α (TNF-α), IL-4, and IL-6. The underlying mechanisms of TUG1 were explored by RNA-binding protein immunoprecipitation (RIP) and dual-luciferase reporter (DLR) assay. TUG1 and HMGB1 were statistically elevated in the tissue of CCI rats, while miR-29b-3p was reduced. TUG1 competitively binds to miR-29b-3p to upregulate HMGB1 levels. Suppression of TUG1 persistently decreased PWL and PWT along with increased frequency of paw-lifting, whereas this alleviation was typically rescued by the abrogated miR-29b-3p. Analogously, knockdown of TUG1 inhibited CCI-induced overproduction of IL-6, IL-1β, and TNF-α, and reduction of IL-4 and IL-6, but this inhibition was partially abrogated by the reduction of miR-29b-3p. Suppression TUG1 can alleviate NP hypersensitivity and neuroinflammation in CCI rats by competitively binding miR-29b-3p to weaken HMGB1.