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

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 <i>RBMS3</i> gene, hsa_circ_0064644) upregulation was examined in OS and was validated <i>in vitro</i> and <i>in vivo</i>, upstream regulator and downstream target of circRBMS3 were both explored. RNA pull down, a luciferase reporter assay, biotin-coupled microRNA capture and fluorescence <i>in situ</i> hybridization were used to evaluate the interaction between circRBMS3 and micro (mi)-R-424-5p. For <i>in vivo</i> 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 <i>in vitro</i> data indicated that ShcircRBMS3 inhibits the proliferation and migration of osteosarcoma cells. Mechanistically, we showed that circRBMS3 could regulate <i>eIF4B</i> and <i>YRDC</i>, through 'sponging' miR-424-5p. Furthermore, knockdown of circRBMS3 inhibited malignant phenotypes and bone destruction of OS <i>in vivo</i>. 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.