circKMT2D contributes to H<sub>2</sub>O<sub>2</sub>‑attenuated osteosarcoma progression via the miR‑210/autophagy pathway

Zhang,Jun; Chou,Xubin; Zhuang,Ming; Zhu,Chenlei; Hu,Yong; Cheng,Dong; Liu,Zhiwei

doi:10.3892/etm.2020.9193

November-2020 Volume 20 Issue 5

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November-2020 Volume 20 Issue 5

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Article Open Access

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

Authors:
- Jun Zhang
- Xubin Chou
- Ming Zhuang
- Chenlei Zhu
- Yong Hu
- Dong Cheng
- Zhiwei Liu
View Affiliations / Copyright

Affiliations: Department of Spine Surgery, The Third Affiliated Hospital of Soochow University, Changzhou 213001, P.R. China

Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 65
|
Published online on: September 9, 2020

https://doi.org/10.3892/etm.2020.9193
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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 (H₂O₂)‑induced OS progression. H₂O₂ (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 H₂O₂, 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 H₂O₂‑treated MG63 cells. In addition, the effects of miR‑210 on the expression of the autophagy‑related proteins Beclin1 and p62 in H₂O₂‑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 H₂O₂‑treated MG63 cell phenotype through autophagy was investigated. The results demonstrated that H₂O₂ 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 H₂O₂‑treated MG63 and U2OS cells. circKMT2D possessed binding sites for miR‑210 and inhibited miR‑210 expression. In H₂O₂‑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 H₂O₂‑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 H₂O₂‑treated MG63 cells. Taken together, these findings indicated that circKMT2D knockdown may contribute to the inhibition of H₂O₂‑attenuated OS progression via miR‑210/autophagy pathway.

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