Abstract
Background
Circular RNAs (circRNAs) have been shown to have critical regulatory roles in tumorigenesis. However, the contribution of circRNAs to OS (osteosarcoma) remains largely unknown.
Methods
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 tumorgenesis experiments, Subcutaneous and Orthotopic xenograft OS mouse models were built.
Results
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 malignant tumor cells. Mechanistically, we show that circRBMS3 can regulate eIF4B and YRDC, through ‘sponging’ miR-424-5p. Furthermore, knockdown of circRBMS3 inhibited malignant phenotypes and bone destruction of OS in vivo.
Conclusions
Our results reveal an important role for a novel circRBMS3 in the growth and metastasis of malignant tumor cells and provide a fresh perspective on circRNAs in OS progression.
Reversibility of acid and alkaline deoxyribonuclease deficiency in malignant tumor cells.
