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

Yang,Huidong; He,Cheng; Feng,Yi; Jin,Jie

doi:10.3892/ol.2023.14157

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

Authors:
- Huidong Yang
- Cheng He
- Yi Feng
- Jie Jin
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Affiliations: Department of Orthopedics, Wuhan Asia General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Orthopedics, The 908th Hospital of Joint Logistics Support Forces of Chinese PLA, Nanchang, Jiangxi 330002, P.R. China
Published online on: November 16, 2023 https://doi.org/10.3892/ol.2023.14157
Article Number: 24
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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