Circ_0007841 knockdown confers cisplatin sensitivity to ovarian cancer cells by down-regulation of NFIB expression in a miR-532-5p-dependent manner

ABSTRACT

Cisplatin (DDP) is first-line management for ovarian cancer (OC). Previous data have suggested that circular RNA_0007841 (circ_0007841) regulates OC progression; however, there is no data on its role in the sensitivity of OC cells to DDP. RNA expression of circ_0007841, microRNA-532-5p (miR-532-5p) and nuclear factor I B (NFIB) was detected by quantitative real-time polymerase chain reaction in OC patient samples and OC cell lines. Protein expression was checked by Western blotting analysis. Cell viability, proliferation, cell apoptotic rate, migration and invasion were investigated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide, 5-Ethynyl-29-deoxyuridine, flow cytometry analysis, scratch test and transwell assays, respectively. The interactions among circ_0007841, miR-532-5p and NFIB were identified by a dual-luciferase reporter assay. Xenograft mouse model assay was performed to determine the effect of circ_0007841 on DDP sensitivity in vivo. Circ_0007841 and NFIB expression were upregulated, whereas miR-532-5p was downregulated in DDP-resistant OC tissues and cells compared with controls. Circ_0007841 silencing improved DDP sensitivity, inhibited cell proliferation, invasion and migration, but induced cell apoptosis in DDP-resistant OC cells. Circ_0007841 acted as a miR-532-5p sponge and regulated DDP resistance and OC cell malignancy through miR-532-5p in DDP-resistant OC cells. Besides, the overexpression of NFIB, a target of miR-532-5p, remitted miR-532-5p-mediated effects in DDP-resistant OC cells. Circ_0007841 depletion conferred DDP sensitivity to DDP-resistant OC cells in vivo. Further, circ_0007841 was secreted from DDP-resistant OC cells through being packaged into exosomes. Circ_0007841 conferred DDP resistance to DDP-resistant OC cells through the miR-532-5p/NFIB axis, suggesting the potential of circ_0007841 as a therapeutic target for OC.

Keywords:

• Ovarian cancer
• circ_0007841
• miR-532-5p
• NFIB
• DDP
• gene therapy

Disclosure statement

No potential conflict of interest was reported by the authors.