Knockdown of circMFN2 inhibits cell progression and glycolysis by miR-198/CUL4B pathway in ovarian cancer.

Abstract

Circular RNA (circRNA) regulates malignant tumors, including ovarian cancer (OC). The present research study aimed to reveal the biological mechanism of circRNA mitofusin 2 (circMFN2) in OC. Cell biological behaviors were investigated using clonogenicity assay, EdU assay, transwell assay, and flow cytometry analysis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analysis were implemented to detect the levels of circMFN2, miR-198, Cullin 4B (CUL4B), and apoptosis-related proteins. Glycolysis was assessed by glucose assay kit, lactate assay kit, and ATP level detection kit. The relationships among miR-198, circMFN2, and CUL4B were verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. The xenograft mice model was used to analyze tumor growth in vivo. The expression of circMFN2 and CUL4B was increased, while miR-330-5p was decreased in OC tissues or cells. TheabsenceofCircMFN2hindered cell proliferation, migration, invasion, and glycolysisand promoted apoptosis in OC cells. We found that circMFN2 promoted CUL4B expression via sponging miR-198. MiR-198 depletion reversed circMFN2 knockdown-induced effects in OC cells. Furthermore, CUL4B overexpression overturned the inhibitory effect of miR-198 in OC cells. And the absence of circMFN2 inhibited tumor growth in vivo. CircMFN2 repressed OC progression by regulating the miR-198/CUL4B axis.