MiR-30a-5p Downregulation Induces Neuronal Autophagy by Activating AMPK After 2856MHz Microwave Radiation
Abstract Background With the development of science and technology, microwaves are being widely used. More and more attention has been paid to the potential health hazards of microwave exposure. The regulation of miR-30a-5p (miR-30a) on autophagy is involved in the pathophysiological process of many diseases. Our previous study found that 30 mW/cm2 microwave radiation could reduce miR-30a expression and activate neuronal autophagy in rat hippocampus. However, the roles played by miR-30a in microwave-induced neuronal autophagy and related mechanisms remain largely unexplored. Results In the present study, we established neuronal damage models by exposing rat hippocampal neurons and rat adrenal pheochromocytoma (PC12) cell-derived neuron-like cells to 30 mW/cm2 microwave, which resulted in miR-30a downregulation and autophagy activation in vivo and in vitro. Bioinformatics analysis was conducted, and Beclin1, Prkaa2, Irs1, Pik3r2, Rras2, Ddit4, Gabarapl2 and autophagy-related gene 12 (Atg12) were identified as potential downstream target genes of miR-30a involved in regulating autophagy. Based on our previous findings that microwave radiation can cause a neuronal energy metabolism disorder, Prkaa2, encoding adenosine 5’-monophosphate-activated protein kinase α2 (AMPKα2, an important catalytic subunit of energy sensor AMPK), was selected for further analysis. Dual-luciferase reporter assay results showed that Prkaa2 is a downstream target gene of miR-30a. Microwave radiation increased the expression and phosphorylation (Thr172) of AMPKα both in vivo and in vitro. Moreover, the transduction of cells with miR-30a mimics suppressed AMPKα2 expression, inhibited AMPKα (Thr172) phosphorylation and reduced autophagy flux in neuron-like cells. Importantly, miR-30a mimics abolished microwave-activated autophagy and inhibited microwave-induced AMPKα (Thr172) phosphorylation. Conclusions AMPKα2 was a newly founded downstream gene of miR-30a involved in autophagy regulation, and miR-30a downregulation after microwave radiation could promote neuronal autophagy by increasing AMPKα2 expression and activating AMPK signaling.