Identification Of A New Role Of miR-199a-5p As Factor Implied In Neuronal Damage: Decreasing The Expression Of Its Target X-Linked Anti-Apoptotic Protein (XIAP) After SCI.

Abstract

Altered expression of microRNAs (miRNAs) after spinal cord injury (SCI) has been described as being responsible for the main secondary responses, such as apoptosis. X-linked inhibitor apoptosis protein (XIAP) is a key apoptotic component involved in the progression of apoptotic programmed cell death. Several regulators have been described to modulate the XIAP's function, including the post-transcriptional regulator's miRNAs. The main aim of the present work is to identify miRNAs with altered expression after SCI which can regulate XIAP expression using bioinformatics and prediction algorithms. Our bioinformatic analyses identified several miRNAs candidates whose up-regulation following SCI could be responsible for the down-regulation of XIAP, including miR-199a-5p. We examined the relationship between miR-199a-5p and XIAP and their negative correlation expression levels after SCI and characterized the spatial distribution of miR-199a-5p in uninjured and rat-contused spinal cords, using a specific fluorescent in situ hybridization (FISH) probe for miR-199a-5p. Finally, in vitro simulation of the increment in miR-199a-5p observed after SCI by transfection of a miR-199a-5p mimic into C6 cells confirmed the decrease in XIAP protein levels.. These findings provide new insights into apoptotic miRNAs-mediated mechanisms after SCI, which will help us develop therapeutic strategies based on miRNAs for treating SCI.