MYC-mediated miR-320a affects receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast formation by regulating phosphatase and tensin homolog (PTEN)

Abstract

ABSTRACT Osteoporosis is a serious bone metabolism disease. Recent studies have shown that MYC could promote the formation of osteoclasts. Evidence has also shown that miR-320a could injure osteoblasts by inducing oxidative stress. By querying the database, we found that MYC has the potential to target and affect the expression of miR-320a. However, the effects of MYC and miR-320a on the the receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclasts are unclear. In this study, we examined the relationship between MYC and miR-320a with luciferase reporter assay. To investigate the role of MYC and miR320a in osteoporosis, MYC or miR-320a expression were knocked down in RAW 264.7 cells. Meanwhile, the expression of markers of osteoclasts was detected with Western blotting. Finally, we inhibited the expression of PTEN in RAW 264.7 cells with miR-320a depletion and detected the expression of abovementioned proteins. MYC promoted the expression of miR-320a in RAW 264.7 cells by binding to the promoter of miR-320a. Inhibition of MYC and miR-320a suppressed the formation of RANKL-induced osteoclasts by inhibiting the expression of c-Fos, NFATc1, TRAP and CTSK. Moreover, the expression of c-Fos, NFATc1, TRAP and CTSK was rescued and the RANKL-induced osteoclasts was promoted after the repressing the expression of PTEN. In conclusion, MYC enhanced the formation of RANKL-induced osteoclasts by modulating the miR-320a/PTEN pathway.