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. The absence of CircMFN2 hindered cell proliferation, migration, invasion, and glycolysis and 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.

The role of circRNAs in regulation of drug resistance in ovarian cancer

“…Similarly, exosome-transmitted circIFNGR2 influenced tumor metastasis via affecting the miR-378/ST5 axis in ovarian cancer ( Chen et al, 2023a ). Downregulation of circMFN2 reduced tumor progression and regulated glycolysis via affecting miR-198 and CUL4B pathway in ovarian cancer ( Song et al, 2023 ). Hsa_circ_0001741 adsorbed the miR-188-5p and increased the expression of FOXN2, contributing to inhibition of cell proliferation in ovarian cancer ( Wang et al, 2023b ).…”