Circ_0004104 Accelerates the Progression of Gastric Cancer by Regulating the miR-539-3p/RNF2 Axis.

BACKGROUND: Circular RNA (circRNA) has been shown to be closely associated with cancer progression, including gastric cancer (GC). However, the function of circ_0004104 in GC progression has not been clarified.

AIMS: The purpose of this study was to explore the role of circ_0004104 in GC progression.

METHODS: The expression levels of circ_0004104, miR-539-3p, and ring finger protein 2 (RNF2) were assessed using quantitative real-time polymerase chain reaction. Cell proliferation was measured by 3-(4,5-dimethyl-2 thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, and cell migration and invasion were detected using transwell assay. The levels of glutamine, glutamate, and α-ketoglutarate were determined to evaluate the glutaminolysis of cells, and the protein levels of glutaminolysis-related markers and RNF2 were detected using western blot analysis. Furthermore, Dual-Luciferase Reporter Assay was employed to assess the interaction between miR-539-3p and circ_0004104 or RNF2. Animal experiments were carried out to evaluate the effect of circ_0004104 silencing on GC tumor growth in vivo.

RESULTS: Circ_0004104 was upregulated in GC, and its knockdown repressed the proliferation, metastasis, and glutaminolysis of GC cells in vitro and reduced GC tumor growth in vivo. Furthermore, we discovered that circ_0004104 could sponge miR-539-3p and miR-539-3p could target RNF2. The rescue experiments suggested that miR-539-3p inhibitor could reverse the suppressive effect of circ_0004104 silencing on GC progression, and RNF2 overexpression also reversed the inhibition effect of miR-539-3p mimic on GC progression.

CONCLUSION: Circ_0004104 accelerated GC progression via regulating the miR-539-3p/RNF2 axis, indicating that circ_0004104 might be a potential therapeutic target for GC.