MicroRNA-299a-5p Protects against Spinal Cord Injury through Activating AMPK Pathway

OBJECTIVE: Inflammation and oxidative stress are implicated in the pathogenesis of spinal cord injury (SCI). The present study is aimed at investigating the function and molecular basis of microRNA-299a-5p (miR-299a-5p) during SCI in mice. METHODS: Mice were exposed to SCI surgery and then intrathecally injected with the agomir, antagomir, or matched negative controls of miR-299a-5p to overexpress or silence miR-299a-5p. To inhibit AMP-activated protein kinase (AMPK), mice were intraperitoneally injected with compound C (CC). To overexpress pH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1), lentiviral vectors were used. RESULTS: The miR-299a-5p expression in the spinal cord was dramatically reduced by SCI stimulation. The miR-299a-5p agomir prevents, while the miR-299a-5p antagomir exacerbates inflammation, oxidative stress, and SCI in mice. Mechanistically, we found that miR-299a-5p directly inhibited PHLPP1 and subsequently activated AMPK pathway. The PHLPP1 overexpression of AMPK inhibition with either genetic or pharmacologic methods dramatically abolished the miR-299a-5p agomir-mediated protective effects against SCI. CONCLUSION: miR-299a-5p protects against spinal cord injury through activating AMPK pathway.