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Updated: Aug 7, 2025

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
A novel circular RNA circRBMS3 regulates proliferation and metastasis of osteosarcoma by targeting miR-424-eIF4B/YRDC
Zhe Gong1, Panyang Shen1, Haitao Wang1
1Department 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.
Abstract:
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.
Insights
Circular RNAs (circRNAs) play a role in osteosarcoma (OS) development. This study identifies circRBMS3 as upregulated in OS, inhibiting tumor growth and metastasis by sponging miR-424-5p.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their regulatory roles in tumorigenesis.
- The specific contribution of circRNAs to osteosarcoma (OS) development and progression is not well understood.
Purpose of the Study:
- To investigate the role of circRNAs in osteosarcoma.
- To identify and characterize a specific circRNA, circRBMS3, in OS progression.
Main Methods:
- CircRNA deep sequencing was performed on OS and chondroma tissues.
- In vitro and in vivo experiments were conducted to assess the function of circRBMS3.
- RNA pull-down, luciferase reporter assays, and microRNA capture were used to explore molecular mechanisms.
- Xenograft mouse models were utilized for in vivo validation.
Main Results:
- CircRBMS3 expression was found to be significantly higher in OS tissues, regulated by ADAR1.
- Knockdown of circRBMS3 inhibited proliferation, migration, and bone destruction in OS cells both in vitro and in vivo.
- CircRBMS3 was shown to sponge miR-424-5p, thereby regulating downstream targets eIF4B and YRDC.
Conclusions:
- CircRBMS3 plays a crucial role in promoting osteosarcoma growth and metastasis.
- CircRBMS3 acts as a molecular sponge for miR-424-5p, influencing key oncogenic pathways.
- This study highlights circRBMS3 as a potential therapeutic target for osteosarcoma.
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