Exosome‑delivered miR‑486‑3p inhibits the progression of osteosarcoma via sponging CircKEAP1/MARCH1 axis components

Accumulating evidence shows that the disruption of competing endogenous RNA (ceRNA) networks plays a significant role in osteosarcoma (OS) initiation and progression. However, the specific roles and functions of the ceRNAs in OS remain unclear. First, differentially expressed MicroRNAs (DEMs) were identified by mining the E-MTAB-1136 and GSE28423 datasets. MiRWalk website was used to predict the target gene of miRNA. OS-associated circular RNA (circRNA) expression profiles were downloaded from the published microarray databases. Gene expression levels were assessed through reverse transcription-quantitative PCR and western blotting. The biological effects of circKEAP1, MicroRNA (miR)-486-3p and membrane-associated RINGCH finger protein 1 (MARCH1) in OS cells were investigated using Cell Counting Kit-8, Transwell, colony formation and wound healing assays. miR-486-3p was aberrantly downregulated in OS tissues and cell lines and was packed with exosomes. miR-486-3p overexpression was shown to inhibit OS cell progression and promoted cell cycle arrest in vitro. In addition, MARCH1 was identified as a direct downstream molecule of miR-486-3p in OS cells. circKEAP1 was found to be upregulated in OS tissues and cells. circKEAP1 was found to have binding sites with miR-486-3p. Mechanistically, circKEAP1 positively regulated MARCH1 expression by sponging miR-486-3p. Exosomal miR-486-3p inhibited the progression of OS by sponging the circKEAP1/MARCH1 axis. These findings may provide a promising treatment approach for OS.

circular KEAP1; competing endogenous RNAs; exosome; membrane-associated RINGCH finger protein 1; microRNA-486-3p; osteosarcoma.