Downregulation of hsa_circ_0000885 suppressed osteosarcoma metastasis and progression via regulating E2F3 expression and sponging miR-16-5p

Abstract

Introduction: Accumulating evidence has shown that circular RNAs (circRNAs) have indispensable functions during tumor progression by regulating gene expression. A previous study found that upregulation of hsa_circ_0000885 indicated a poor clinical outcome of osteosarcoma (OS). However, the regulatory mechanism of this process is unclear. Methods: This investigation aimed to elucidate how hsa_circ_0000885 regulated OSs. The study used RT-qPCR to investigate hsa_circ_0000885 expression in OS cells. We conducted luciferase reporter assays and analyses to confirm the hsa_circ_0000885 downstream target. We transfected OS cells using different vectors and used Transwell migration, colony formation, western blotting, Matrigel invasion, proliferation, in vivo tumorigenesis, and metastasis assays to identify the role of hsa_circ_0000885 in OS. Results: The results showed that hsa_circ_0000885 expression altered OS cell lines, and that hsa_circ_0000885 downregulation suppressed OS cell proliferation and invasion using in vivo and in vitro experiments. Luciferase reporter assays verified that miR-16-5p and E2F3 were downstream targets of hsa_circ_0000885. E2F3 overexpression or miR-16-5p inhibition reversed OS cell invasion and proliferation after silencing hsa_circ_0000885. Furthermore, hsa_circ_0000885 affected cancer stem cell differentiation by regulating miR-16-5p/E2F3. Conclusions: Overall, the results showed that hsa_circ_0000885 downregulation suppressed OS progression and metastasis via regulating E2F3 expression and sponging miR-16-5p.

Keywords

• Osteosarcoma
• hsa_circ_0000885
• miR-16-5p
• E2F3
• Cancer stem cell