MicroRNA-466c-3p exerts protective effect on neuronal apoptosis and improves functional recovery post spinal cord injury via mitochondrial apoptotic pathway

• Published in: AMB Express Vol. 10; no. 1; p. 113
• Main Authors: An, Yan, Li, Jianing, Yuan, Qiang, Fan, Mingxing
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 15.06.2020; Springer Nature B.V; SpringerOpen
• Subjects: Apoptosis; Bcl-2; Bcl-2 protein; Biomedical and Life Sciences; Biotechnology; Cell size; Hydrogen peroxide; Life Sciences; Locomotor activity; Microbial Genetics and Genomics; Microbiology; Microglia; miR-466c-3p; miRNA; Mitochondria; Original; Original Article; Oxidative stress; Recovery; Recovery of function; Spinal cord injuries; Spinal cord injury; Staining; Transfection; Bcl-2; miR-466c-3p; Spinal cord injury; Apoptosis
• ISSN: 2191-0855; 2191-0855
• DOI: 10.1186/s13568-020-01033-3

Spinal cord injury (SCI) is involved with abnormal expression of miRNAs (miRs) which are responsible for some II ry injury responses which include apoptosis, inflammation and oxidative stress. Mechanisms involving miRs induced apoptosis still needs to be investigated. In the present work we developed a rat model of SCI, followed by microarray analysis for expression of miRs at various time points after SCI. The locomotor activity was assessed by Basso, Beattie and Bresnahan score, lesion volume was analyzed by cresyl violet staining and TUNEL staining for extent of apoptosis at various time points of post SCI. Numbers of miRs were altered after 2 weeks of SCI among which miR-466c-3p was the most significantly down-regulated. Transfection with miR-466c-3p mimics caused overexpression of miR-466c-3p, also improvement in functional recovery, decrease in apoptosis of neuronal cells and lesion size was observed in SCI rats. The Luciferase assay suggested that miR-466c-3p suppressed the expression of Bcl-2 (apoptosis regulator). It was also evidenced that upon restoring the levels of Bcl-2 with the help of pc-DNA3-Bcl-2 halted the attenuating action of miR-466c-3p in hydrogen peroxide exposed N9 microglia cells. The findings suggested that miR-466c-3p may inhibit mitochondrial apoptotic pathway via blocking Bcl-2 and cleaved capase-9/-3in rats after SCI. Altogether, the results suggested that miR-466c-3p may exert attenuating effect on functional recovery and inhibit the apoptosis of neuronal cells via halting the mitochondrial apoptosis cascade in SCI rats indicating that miR-466c-3p can be attractive therapeutic candidate in treating SCI.