Circ-FOXM1 promotes the proliferation, migration and EMT process of osteosarcoma cells through FOXM1-mediated Wnt pathway activation

Abstract

Background Osteosarcoma (OS) is a malignant bone tumor that commonly occurs in adolescents with a high mortality rate and frequent pulmonary metastasis. Emerging evidence has suggested that circular RNAs (circRNAs) are important regulators in multiple biological activities of carcinomas. Nevertheless, the role of circRNAs derived from forkhead box M1 (FOXM1), a well-accepted modulator of OS progression, has not been discussed in OS. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to test circ-FOXM1 (hsa_circ_0025033) expression in OS cell lines. Cell counting kit-8 (CCK-8), 5-ethynyl-2’-deoxyuridine (EdU), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), transwell assays and western blot analysis of epithelial-mesenchymal transition (EMT) markers were conducted to evaluate cell proliferation, apoptosis, migration, and EMT process. Luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) assay were utilized to detect the interaction of circ-FOXM1 and RNAs. Results High expression of circ-FOXM1 was detected in OS cell lines. Functionally, circ-FOXM1 knockdown inhibited the proliferation, migration and EMT process, whereas induced the apoptosis of OS cells. From the aspect of molecular mechanism, circ-FOXM1 was discovered to upregulate FOXM1 expression via sponging miR-320a and miR-320b, therefore activating Wnt signaling pathway. Besides, rescue experiments elucidated that circ-FOXM1 regulated cellular activities of OS cells via FOXM1. Further, in vivo assays supported that loss of circ-FOXM1 restrained OS tumor growth. Conclusion Circ-FOXM1 facilitated the malignant phenotypes of OS cells through FOXM1-mediated Wnt pathway activation, revealing circ-FOXM1 as a potential biomarker for OS treatment.

Overexpression of FoxM1 Enhanced the Protective Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Lipopolysaccharide-Induced Acute Lung Injury through the Activation of Wnt/β-Catenin Signaling

“…Likewise, Chen et al [ 64 ] found that Wnt-induced deubiquitination of FoxM1 is a novel and important mechanism controlling canonical Wnt signaling and cell proliferation. Furthermore, FoxM1-mediated activation of the Wnt pathway can promote cell proliferation, migration, and epithelial-mesenchymal transition [ 65 ]. Here, we discovered that β -catenin expression lowered following LPS therapy but was reversed by BMSCs-Vector or BMSCs-FoxM1, and the reversal was more pronounced with BMSCs-FoxM1.…”

Signal Pathways and microRNAs in Osteosarcoma Growth and the Dual Role of Mesenchymal Stem Cells in Oncogenesis

“…miRNAs: It has been shown that miR-320a and miR-320b function as OS inhibitors [91,92]. Overexpression of these miRs promotes downregulation of FOXM1 expression in OS cells [93]. Low expression of miR-361-5p was observed in OS tissues and cell lines.…”