MicroRNA-381/Hes1 is a potential therapeutic target for spinal cord injury

Abstract

The aim of the present study was to investigate whether microRNA-381 is a potential therapeutic target for spinal cord injury (SCI) and its possible mechanism. Reverse transcription quantitative polymerase chain reaction (qPCR) for mRNA expression was used to analyze the changes of microRNA-381 expression. Cell viability and cell apoptosis were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Caspase-3 activity was measured using caspase-3 activity kit, and western blot analysis was used to measure the protein expression of neurogenic locus notch homolog protein 1 (Notch1), notch 1 intracellular domain (NICD) and transcription factor HES-1 (Hes1). The data showed that microRNA-381 expression of model SCI rats was downregulated compared with that of control rats. Overexpression of microRNA-381 promoted cell proliferation, and inhibited apoptosis and caspase-3 and apoptosis regulator BAX (Bax) protein expression in neurocytes. Overexpression of microRNA-381 also increased Wnt and β-catenin protein expression, and suppressed the protein expression of Notch1, NICD and Hes1 in neurocytes. Wnt inhibitor, Wnt-C59 (1 μmol/l), inhibited cell proliferation, promoted apoptosis and caspase-3 and Bax protein expression, suppressed β-catenin protein expression and induced Hes1 protein expression in neurocytes following microRNA-381 overexpression. Notch inhibitor, FLI-06 (1 μmol/l), promoted cell proliferation, inhibited apoptosis and caspase-3 and Bax protein expression, and suppressed NICD and Hes1 protein expression in neurocytes following microRNA-381 overexpression. Thus, this study showed that overexpression of microRNA-381 promotes cell proliferation of neurocytes in SCI via Hes1 expression, which may be a novel important mechanism for SCI in clinical applications.