circKMT2D contributes to H₂O₂‑attenuated osteosarcoma progression via the miR‑210/autophagy pathway

Abstract

Circular RNAs (circRNAs) have been demonstrated to be involved in osteosarcoma (OS) development; however, the underlying mechanism of circKMT2D in OS progression remains unclear. The present study aimed to elucidate how circKMT2D could affect hydrogen peroxide (H 2 O 2)-induced OS progression. H 2 O 2 (100 µmol/l) was used to treat MG63 and U2OS cells. The cell viability, invasive ability, apoptosis and circKMT2D expression were detected using Cell Counting Kit-8 assay, Transwell assay, flow cytometry and reverse transcription-quantitative PCR, respectively. Furthermore, MG63 and U2OS cells transfected with circKMT2D short hairpin RNA and negative control were treated with H 2 O 2 , and circKMT2D expression and cell phenotype were determined. Dual-luciferase reporter assay was conducted to determine the association between circKMT2D and miR-210 expression level. Rescue experiments were conducted to examine the mechanisms through which circKMT2D and miR-210 could affect H 2 O 2-treated MG63 cells. In addition, the effects of miR-210 on the expression of the autophagy-related proteins Beclin1 and p62 in H 2 O 2-treated MG63 cells were detected by western blotting. An autophagy inhibitor was used to treat the MG63 cells, and whether miR-210 could affect the H 2 O 2-treated MG63 cell phenotype through autophagy was investigated. The results demonstrated that H 2 O 2 treatment promoted cell apoptosis and decreased cell viability, invasive ability and circKMT2D expression in MG63 and U2OS cells. Furthermore, circKMT2D knockdown decreased the cell viability and invasive ability and enhanced the apoptosis of H 2 O 2-treated MG63 and U2OS cells. circKMT2D possessed binding sites for miR-210 and inhibited miR-210 expression. In H 2 O 2-treated MG63 cells, miR-210 silencing partially reversed the circKMT2D knockdown-induced cell viability inhibition and apoptosis promotion. In addition, miR-210 elevated Beclin1 expression and decreased p62 expression in H 2 O 2-treated MG63 cells. The use of the autophagy inhibitor partially reversed the miR-210 overexpression-induced promotion of apoptosis and inhibition of the viability and invasive ability of H 2 O 2-treated MG63 cells. Taken together, these findings indicated that circKMT2D knockdown may contribute to the inhibition of H 2 O 2-attenuated OS progression via miR-210/autophagy pathway.

miR-210 promotes hepatocellular carcinoma progression by modulating macrophage autophagy through PI3K/AKT/mTOR signaling

“…2 ). Zhang et al [ 25 ] screened some key genes involved in the development of osteosarcoma, including miRNAs, which may be related to the metastasis of osteosarcoma. They found miR-210 overexpression elevated Beclin-1 expression and decreased p62 expression in osteosarcoma cells.…”

Circular RNA-regulated autophagy is involved in cancer progression

“…The miR-432-5p/HDAC4 axis has been shown to mediate the oncogenic roles of circCRIM1. Zhang et al (2020b) found that H 2 O 2 refrained the progression of osteosarcoma, while upregulating the circKMT2D in osteosarcoma. Following explorations demonstrated that silencing circKMT2D markedly impaired the viability and metastasis of osteosarcoma, while activating the autophagy process and strengthening the anti-cancer effect of H 2 O 2 .…”

Prognostic value of circWWC3 as a novel survival‑related biomarker for clear cell renal cell carcinoma

“…circRNAs have three main functions: i) Serving as microRNA (miR/miRNA) sponges to sequester and inhibit miRNA activity; ii) acting as regulators that interact with proteins; iii) serving as templates for protein synthesis (8). circRNAs play an important role in the development and progression of human tumors, according to accumulating evidence (9)(10)(11).…”