Circ-FOXM1 Promotes Cell Proliferation, Migration and EMT Process in Osteosarcoma Through FOXM1-Mediated Wnt Pathway Activation

Abstract Background: As the most common primary bone tumor in adolescents and children, osteosarcoma commonly occurs with high mortality rate and metastasis. Emerging evidence has illustrated that circular RNAs (circRNAs) are important regulatory RNAs that are involved in multiple biological activities of carcinomas. Circ-FOXM1 (hsa_circ_0025033) is a recently found circRNA and promotes the cellular activities of several cancers. However, the function and molecular mechanism of circ-FOXM1 in osteosarcoma have not been interrogated yet. Methods: The qRT-PCR was utilized to test the expression of circ-FOXM1 in osteosarcoma cell lines. Loss-of-function assays including CCK-8, EdU, TUNEL, transwell and western blot assays were conducted to measure cell proliferation, cell migration, EMT process and cell apoptosis. Luciferase reporter assay and RIP assay were utilized to detect the interaction of circ-FOXM1 and RNAs. Results：We discovered the high expression of circ-FOXM1 in osteosarcoma cells. Besides, it was indicated that circ-FOXM1 knockdown inhibited cell proliferation, cell migration and EMT process, as well as induced cell apoptosis of osteosarcoma cells. Furthermore, circ-FOXM1 was discovered to upregulate the expression level of forkhead box M1 (FOXM1) at post-transcriptional level. Moreover, it was proved that circ-FOXM1 sponged miR-320a and miR-320b so as to increase FOXM1 expression. Additionally, circ-FOXM1 could activate Wnt signaling pathway through upregulating FOXM1. In the end, rescue assays certified that FOXM1 overexpression could totally rescue the circ-FOXM1 silence-repressed cellular activities of osteosarcoma cells.Conclusion: Circ-FOXM1 facilitated the progression of osteosarcoma cells via relieving FOXM1 from the inhibition by miR-320a and miR-320b.