MicroRNA-10b suppresses the migration and invasion of chondrosarcoma cells by targeting brain-derived neurotrophic factor

Abstract

MicroRNAs (miRs) can lead to mRNA degradation or inhibit protein translation through directly binding to the 3'-untranslational region (UTR) of their target mRNAs. Deregulation of miR-10b has been reported to be associated with chondrosarcoma. However, the role of miR-10b in chondrosarcoma cell migration and invasion, as well as the underlying mechanisms, has not been investigated. In the present study, it was demonstrated that miR-10b was notably downregulated in the JJ012 and SW1353 chondrosarcoma cell lines compared with the TC28a2 normal chondrocyte line. Treatment with DNA demethylating agent 5-aza-2'-deoxycytidine and histone deacetylase inhibitor 4-phenylbutyric acid, or transfection with miR-10b mimics promoted the expression of miR-10b, which further suppressed the migratory and invasive capacities of JJ012 chondrosarcoma cells. Moreover, brain-derived neurotrophic factor (BDNF) was identified as a novel target of miR-10b, and its protein expression level was negatively regulated by miR-10b in JJ012 cells. Furthermore, overexpression of BDNF reversed the inhibitory effect of miR-10b upregulation on the migration and invasion of JJ012 cells. In addition, the data suggest that matrix metalloproteinase 1 (MMP1) may be involved in the miR-10b/BDNF-mediated chondrosarcoma cell migration and invasion in JJ012 cells. In conclusion, these findings suggest that miR-10b/BDNF may serve as a potential therapeutic target for chondrosarcoma.