Circular RNA circMRPS35 regulates progression and autophagy in osteosarcoma cells by recruiting KAT6B to govern FOXO3

Osteosarcoma serves as frequently occurred bone malignancy that displays low survival rate and high incidence of metastasis. Circular RNAs (circRNAs) have been reported as the crucial molecules in osteosarcoma development. However, the effect of circRNA circMRPS35 on osteosarcoma remains unclear. Here, we aimed to explore the function of circMRPS35 in the regulation of autophagy and progression of osteosarcoma. The colony formation numbers and Edu-positive osteosarcoma cells were repressed by the overexpression of circMRPS35. Meanwhile, the overexpression of circMRPS35 increased the apoptosis rate of osteosarcoma cells. The expression levels of autophagy markers, including LC3 and Beclin1, were enhanced by the overexpression of circMRPS35 in osteosarcoma cells. Mechanically, the depletion of circMRPS35 reduced the enrichment of histone H3 lysine 23 acetylation (H3K23ac) on forkhead box O3 (FOXO3) promoter in osteosarcoma cells. The interaction of circMRPS35 and KAT6B was identified. The knockdown of KAT6B reduced the enrichment of H3K23ac on FOXO3 promoter in osteosarcoma cells. The depletion of circMRPS35 repressed the expression of FOXO3 in the MG63 and MNNG/HOS cells, whereas the overexpression of KAT6B reversed the effect. Significantly, KAT6B promotes apoptosis and autophagy of osteosarcoma cells. The overexpression of circMRPS35 induced the apoptosis and autophagy of osteosarcoma cells, in which the depletion of KAT6B or FOXO3 reversed the effect. The overexpression of circMRPS35 inhibited the tumor growth in vivo , whereas the depletion of KAT6B could reverse the effect in the mice. Therefore, we concluded that circRNA circMRPS35 repressed progression and induced autophagy of osteosarcoma cells.