Background
Renal cell carcinoma (RCC) is a common lethal urological malignancy. Circular RNAs are assumed to play important roles in cancer development. The
Conclusions
Circ_0008717 aggravated the progression of RCC by activating FBXO17 through targeting miR-217, which provided a novel mechanism for circ_0008717 to participate in RCC progression.
Methods
The expression of circ_0008717, miR-217 and F-box protein 17 (FBXO17) mRNA was detected by a real-time quantitative polymerase chain reaction. Cell proliferation was examined using a cell counting kit-8 assay and an 5-ethynyl-2'-deoxyuridine assay. Cell apoptosis was assessed by a flow cytometry assay. Cell migration and cell invasion were investigated using a transwell assay. Glycolysis progression was assessed according to the levels of glucose uptake and lactate production. The expression of glycolysis-related proteins and FBXO17 protein was quantified by western blotting. The targets were analyzed by the bioinformatics tools (starBase and circinteractome) and validated by a dual-luciferase reporter assay, RNA pull-down assay and RNA immunoprecipitation assay. A xenograft model was established to monitor the role of circ_0008717 in vivo.
Results
Circ_0008717 was upregulated in RCC tissues and cells. Silencing circ_0008717 suppressed RCC cell proliferation, migration, invasion and glycolysis but promoted cell apoptosis. MiR-217 was a target of circ_0008717 and bound to the FBXO17 3' untranslated region. The expression of FBXO17 was positively regulated by circ_0008717 but impaired by miR-217 reintroduction. The inhibitory effects of circ_0008717 knockdown on RCC cell malignant behaviors were reversed by miR-217 inhibition or FBXO17 overexpression. Circ_0008717 knockdown inhibited tumor growth in vivo by regulating miR-217 and FBXO17. Conclusions: Circ_0008717 aggravated the progression of RCC by activating FBXO17 through targeting miR-217, which provided a novel mechanism for circ_0008717 to participate in RCC progression.