Abstract
MicroRNAs (miRs) have been observed to be involved in the modulation of various physiopathological processes. However, the impacts of miRNAs on muscle atrophy have not been fully investigated. In the present study, the results demonstrated that miR-351 was differentially expressed in the tibialis anterior (TA) muscle at various times following sciatic nerve transection, and the time-dependent expression profile of miR-351 was inversely correlated with that of tumor necrosis factor receptor-associated factor 6 (TRAF6) at the mRNA and protein levels. The dual luciferase reporter assay indicated that miR-351 was able to significantly downregulate the expression levels of TRAF6 by directly targeting the 3'-untranslated region of TRAF6. Overexpression of miR-351 inhibited a significant decrease in the wet weight ratio or cross-sectional area of the TA muscle following sciatic nerve transection. Western blot analysis indicated that the protein expression levels of TRAF6, muscle ring-finger protein 1 (MuRF1) and muscle atrophy F-box (MAFBx) in denervated TA muscles were suppressed by overexpression of miR-351. These results demonstrate that miR-351 inhibits denervation-induced atrophy of TA muscles following sciatic nerve transection at least partially through negative regulation of TRAF6 as well as MuRF1 and MAFBx, the two downstream signaling molecules of TRAF6.
Keywords:
denervation; microRNA-351; muscle atrophy; negative regulation; tumor necrosis factor receptor-associated factor 6.