Circ-FOXM1 contributes to cell proliferation, invasion, and glycolysis and represses apoptosis in melanoma by regulating miR-143-3p/FLOT2 axis

Abstract

Background: Numerous literatures have demonstrated that circular RNAs (circRNAs) are involved in multiple types of tumors. However, the effects of circRNAs in melanoma are not very clear. In this study, we aimed to investigate the roles and mechanisms of circ-FOXM1 in melanoma. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the expression of circ-FOXM1, microRNA-143-3p (miR-143-3p), and Flotillin 2 (FLOT2) mRNA. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flow cytometry analysis, and transwell assay were employed to test cell proliferation, apoptosis, and invasion, respectively. The glucose consumption and lactate production were examined by specific kits. Western blot assay was utilized for the detection of hexokinase2 (HK2), pyruvate kinase isozyme type M2 (PKM2), and FLOT2. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to verify the targeting association between miR-143-3p and circ-FOXM1 or FLOT2. A murine xenograft model was established to explore the effect of circ-FOXM1 in vivo. Results: Circ-FOXM1 was elevated and miR-143-3p was reduced in melanoma tissues and cells. Circ-FOXM1 deficiency impeded cell proliferation, invasion, and glycolysis and facilitated cell apoptosis in melanoma in vitro and tumorigenesis in vivo. Circ-FOXM1 acted as a sponge of miR-143-3p and the impacts of circ-FOXM1 silencing on cell proliferation, apoptosis, invasion, and glycolysis were overturned by miR-143-3p deletion. Moreover, FLOT2 was a target gene of miR-143-3p and FLOT2 overexpression rescued the inhibitory effect of miR-143-3p on melanoma progression. Conclusion: Circ-FOXM1 facilitated the development of melanoma by upregulating FLOT2 through miR-143-3p.