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

Abstract

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.

Non-coding RNAs are involved in tumor cell death and affect tumorigenesis, progression, and treatment: a systematic review

“…Knockdown of circRNA TOPBP1-interacting checkpoint and replication regulator (circTICRR) expression activates autophagy in cervical cancer cells; circTICRR binds to F287/F289 in the ribonucleotide reductase regulatory subunit M3 domain of human antigen R (HuR) and increases the expression of glutamate dehydrogenase 1 (GLUD1) protein, ultimately promoting autophagy ( Zhu et al, 2022 ). circMRPS35 increases microtubule associated protein 1 light chain 3 (LC3) and Beclin-1 expression to promote autophagy in osteosarcoma cells ( Jiang C. et al, 2022 ). After downregulation in osteosarcoma cells, circCRIM1 inhibits cell proliferation, promotes cell autophagy, and acts on the miR-432-5p/HDAC4 axis to inhibit osteosarcoma growth ( Liu J. et al, 2020 ).…”

Regulation of autophagy by circular RNAs in rheumatoid arthritis: Potential targets of action

“…On the one hand, circRNAs regulate autophagy by targeting FOXO to participate in disease pathogenesis. CircMRPS35 induces autophagy in osteosarcoma by recruiting lysine acetyltransferase KAT7 to target FOXO3 modification 88 . CircPAN3 promotes fibrosis in a rat model of myocardial infarction through activation of autophagy by FOXO3/ATG7 89 .…”

The emerging roles of circular RNA-mediated autophagy in tumorigenesis and cancer progression

“…Chen and colleagues demonstrated the pro-autophagic and oncogenic effects of circUBAP2 in CRC, which regulates the expression of miR-582-5p-targeted FOXO1 by sponging this circRNA [ 74 ]. circMRPS35 induces autophagy in osteosarcoma via interacting with KAT6B, and further promoting FOXO3 expression [ 75 ].…”