miR-181a promotes apoptosis in contusion spinal cord injury rats through targeting Bcl-2

Many studies demonstrated that apoptosis would aggravate the secondary injury to the spinal cord and reduced apoptosis can improve the functional recovery after spinal cord injury (SCI). In many animal models and cell types, microRNAs (miRNA) have been implicated as effectors of SCI. However, little is known about the role of microRNAs in the regulation of apoptosis and molecular mechanism in SCI. This paper aims to explore the correlation between reactive oxygen species (ROS)-induced cell apoptosis and dysregulation of microRNAs after SCI. We analyzed six miRNA expression patterns at 1, 3 and 7 days following rat SCI using reverse transcription quantitative PCR (RT-qPCR). Because miR-181a was one of the six miRNAs being most significantly upregulated, we investigated its function. The immortalized murine BV-2 cells were treated with H2O2. The results demonstrated that H2O2 significantly enhanced ROS production, reduced cell viability and induced BV-2 cell apoptosis. We also found that H2O2 significantly enhanced miR-181a expression in a dose-and time-dependent manner. Following miR-181a silencing, H2O2-induced cell viability and apoptosis were rescued in BV-2 cells, and the levels of Caspase 3\8\9 were enhanced in BV-2 cells treated with H2O2. Furthermore, Bcl-2 was identified as a direct target of miR-181 using a Luciferase reporter assay, RT-qPCR and Western blot analysis. Based on previous studies, it was predicted that miR-181a contributed to apoptosis in murine BV-2 cells by regulating the expression of Bcl-2. This proposes a therapeutic target for enhancing neural cell functional recovery after SCI.