Inhibition of long non-coding RNA IGF2AS has profound effect on inducing neuronal growth and protecting local-anesthetic induced neurotoxicity in dorsal root ganglion neurons

Background: Long non-coding RNA IGF2AS was initially identified as a cancer regulator in wilm's tumors. In this study, IGF2AS was investigated of its functions in inducing neural development and protecting local-anesthetic induced neurotoxicity in dorsal root ganglion (DRG) in spinal cord. Methods: Explant of mouse spinal cord DRG was transfected with IGF2AS specific siRNA. The effect of IGF2AS inhibition on neural development was assessed by neurite growth assay, qRT-PCR and western blot assay, respectively. IGF2AS-downregulated DRG explant was then exposed to local anesthetic agent, lidocaine in vitro. The possible protective effects of IGF2AS inhibition on lidocaine-induced DRG neuron apoptosis and neurite loss were further assessed by TUNEL assay, neurite growth assay, qRT-PCR and western blot assays. Results: SiRNA-mediated IGF2AS inhibition promoted neuronal growth, and induced IGF2, BDNF and NT3 upregulations at both gene and protein expressions. In lidocaine-exposed DRG neurons, endogenous IGF2AS inhibition was effective to protect local-anesthetic induced neuronal apoptosis and neurite loss. Further molecular characterization demonstrated that the neuronal protection of IGF2AS inhibition was also associated with upregulations of IGF2, BDNF and NT3 in DRG neurons. Conclusions: Inhibiting endogenous IGF2AS may promote neuronal growth and protect local-anesthetic induced neurotoxicity in DRG neurons, possibly through complimentary IGF2 upregulation and autocrine activation neurotrophin genes. (C) 2016 Published by Elsevier Masson SAS.