MicroRNA-489-3p inhibits neurite growth by regulating PI3K/AKT pathway in spinal cord injury.

Abstract

Spinal cord injury (SCI) is caused by mechanical disruption of the spinal cord. This primary injury is followed by a devastating secondary SCI. It has been shown that various microRNAs (miRNAs) are involved in secondary SCI. The present study explored the role of miR-489-3p on secondary SCI, and its underlying mechanisms. First, we determined the expression of miR-489-3p in blood samples of SCI patients and healthy controls. Further experiments were performed on human neural cell lines, treated with bupivacaine to induce neuron damage. The cultured neural cells were transfected with miR-489-3p mimic, ASO-miR-489-3p or negative control. We then measured cell proliferation and apoptosis in cultured neurons, followed by measurement of neurite outgrowth. After confirming NAA10 as a target gene for miR-489-3p, we measured expression of NAA10 in neurons transfected with miR-489-3p. Finally, we evaluated the effects of miR-489-3p on the PI3K/AKT signal pathway. miR-489-3p was highly expressed in SCI patients and in bupivacaine-treated injured neurons. In cell model, miR-489-3p inhibited proliferation of neurons and promoted apoptosis. miR-489-3p and bupivacaine synergistically inhibited neurite growth. NAA10 gene was negatively regulated by miR-489-3p. Overexpression of NAA10 reversed the effects of miR-489-3p on neurons. Lastly, we found that the inhibitory effects of miR-489-3p on neurons are mediated via activation of the PI3K/AKT pathway. Inhibition of PI3K/AKT pathway using miR-489-3p inhibitor reversed the effects of miR-489-3p on neurons.