Background: Ovarian cancer (OC) is the main cause of cancer-related death in women, and drug resistance is a leading cause of treatment failure. Recently, the involvement of circular RNAs (circRNAs) in cancer progression has become an area of increased investigation. The objective of this study is to uncover the function and regulatory mechanism of circ_0025033 in paclitaxel (PTX)-resistant OC cells.
Methods: The expression of circ_0025033, FOXM1 and miR-532-3p was investigated using quantitative real-time polymerase chain reaction (qRT-PCR), and the protein expression of FOXM1 was quantified by western blot. Cell biological functions, including cell viability, migration/invasion and apoptosis, were explored using 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays, transwell assays and flow cytometry assays. The interaction between miR-532-3p and circ_0025033 or FOXM1 predicted by bioinformatics analysis was validated by pull-down assay and dual-luciferase reporter assay. Exosomes were isolated to determine the further function of circ_0025033.
Result: Circ_0025033 and FOXM1 were highly expressed, while miR-532-3p was poorly expressed in OC tissues and cells, and the expression pattern was greater in PTX-resistant OC cells. Circ_0025033 knockdown lessened PTX resistance, suppressed migration/invasion and promoted apoptosis of PTX-resistant cells. With respect to mechanism, circ_0025033 upregulated the expression of FOXM1 by targeting miR-532-3p, and circ_0025033 knockdown blocked the malignant activities of PTX-resistant OC cells by enriching miR-532-3p and suppressing FOXM1. Exosomes derived from PTX-resistant cells with circ_0025033 knockdown also could repress the malignant actions of PTX-resistant OC cells.
Conclusion: Circ_0025033 downregulation impaired PTX resistance and malignant activities of PTX-resistant OC cells by regulating the miR-532-3p/FOXM1 network.
Keywords: FOXM1; circ_0025033; miR-532-3p; ovarian cancer; paclitaxel.