Research Paper Volume 15, Issue 5 pp 1564—1590

A novel circular RNA circRBMS3 regulates proliferation and metastasis of osteosarcoma by targeting miR-424-eIF4B/YRDC axis

Zhe Gong1, *, , Panyang Shen1, *, , Haitao Wang1, *, , Jinjin Zhu1, , Kaiyu Liang1, , Kefan Wang1, , Yunfeng Mi2, , Shuying Shen1, , Xiangqian Fang1, , Gang Liu1, ,

  • 1 Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University and Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou 310016, Zhejiang Province, China
  • 2 Department of Orthopaedic Surgery, Ningbo First Hospital, Ningbo 315010, China
* Equal contribution

Received: June 9, 2022       Accepted: January 23, 2023       Published: March 9, 2023
How to Cite

Copyright: © 2023 Gong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Circular RNAs (circRNAs) have been demonstrated to have critical regulatory roles in tumorigenesis. However, the contribution of circRNAs to OS (osteosarcoma) remains largely unknown. circRNA deep sequencing was performed to the expression of circRNAs between OS and chondroma tissues. The regulatory and functional role of circRBMS3 (a circRNA derived from exons 7 to 10 of the RBMS3 gene, hsa_circ_0064644) upregulation was examined in OS and was validated in vitro and in vivo, upstream regulator and downstream target of circRBMS3 were both explored. RNA pull down, a luciferase reporter assay, biotin-coupled microRNA capture and fluorescence in situ hybridization were used to evaluate the interaction between circRBMS3 and micro (mi)-R-424-5p. For in vivo tumorigenesis experiments, Subcutaneous and Orthotopic xenograft OS mouse models were built. Expression of circRBMS3 was higher in OS tissues due to the regulation of adenosine deaminase 1-acting on RNA (ADAR1), an abundant RNA editing enzyme. Our in vitro data indicated that ShcircRBMS3 inhibits the proliferation and migration of osteosarcoma cells. Mechanistically, we showed that circRBMS3 could regulate eIF4B and YRDC, through ‘sponging’ miR-424-5p. Furthermore, knockdown of circRBMS3 inhibited malignant phenotypes and bone destruction of OS in vivo. Our results reveal an important role for a novel circRBMS3 in the growth and metastasis of malignant tumor cells and offer a fresh perspective on circRNAs in OS progression.


OS: Osteoarthritis; CircRNAs: Circular RNA; ADAR1: adenosine deaminase 1-acting; CeRNAs: Competing endogenous RNAs; MREs: MicroRNA response elements; RNA-seq: RNA-sequencing; qRT-PCR: Quantitative real-time polymerase chain reaction; RIP: RNA immunoprecipitation; FISH: Fluorescent In Situ Hybridization; CISH: Chromogenic in situ hybridization; ESCC: Esophageal squamous cell carcinoma; NPC: Nasopharyngeal cancer; LSCC: Lung squamous cell carcinoma; DHX9: DExH-Box Helicase 9; EIF4B: eukaryotic translation initiation factor 4B; YRDC: N6-threonylcarbamoyltransferase domain containing.

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