Circ_0008717 promotes renal cell carcinoma progression by upregulating FBXO17 via targeting miR‐217

Abstract

Background Renal cell carcinoma (RCC) is a common lethal urological malignancy. Circular RNAs are assumed to play important roles in cancer development. The objective of the present study was to investigate the role and action mechanism of circ_0008717 in RCC. 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.

hsa_circ_0003596, as a novel oncogene, regulates the malignant behavior of renal cell carcinoma by modulating glycolysis

“…circRNA influences the transcription, protein stability and enzyme activity of key enzymes and transporters of RCC glycolysis by regulating downstream target genes, and participates in glucose metabolism. CircME1 and circ_0008717 promote glycolysis in clear cell RCC [ 21 , 22 ]. This study discovered a new circRNA (hsa_circ_0003596, circCOL5A).…”

An integrated bioinformatics approach to identify key biomarkers in the tubulointerstitium of patients with focal segmental glomerulosclerosis and construction of mRNA–miRNA-lncRNA/circRNA networks

“…Furthermore, hsa-miR-153-3p may be involved in the development of diabetic nephropathy [ 57 ]. miR-217 is associated with a variety of kidney diseases, such as tubular fibrosis [ 58 ] and renal cell carcinoma [ 59 ]. The MALAT1/miR-145/focal adhesion kinase (FAK) pathway was also confirmed to play an important role in TGF-β1-induced renal fibrosis [ 60 ].…”

Non-coding RNAs as potential biomarkers in osteosarcoma

“…It was found that circ_0008717 and lung metastasis are independent prognostic factors through Cox multivariate regression analysis. After knocking down the expression of circ_0008717, the proliferation, migration and invasion of tumor cells can be reduced, and apoptosis can be promoted ( Shen et al, 2022 ). circ_0081001 was another potential biomarker of OS prognosis, which was selected from chemotherapy and chemotherapy-sensitive OS cell lines, showing high levels in advanced OS, chemotherapy-resistant and lung metastasis ( Wei et al, 2021 ) ( Figures 2 , 3 ).…”