MicroRNA-223 promotes hepatocellular carcinoma cell resistance to sorafenib by targeting FBW7

Hepatocellular carcinoma (HCC) is a globally prevalent malignancy associated with a poor patient prognosis. We investigated the relationship between microRNA-223 (miR-223) expression and the sensitivity of HCC cells to sorafenib treatment. miR-223 expression was determined in HCC cell lines with differential sorafenib sensitivity using reverse transcription-quantitative PCR. miR-223 inhibitor, miR-223 mimic, and F-box and WD repeat domain-containing 7 (FBW7) short interfering RNAs (siRNAs) were transfected into the HCC cells to regulate the expression levels of miR-223 and FBW7. Cell proliferation was evaluated using an ethynyl deoxyuridine (EdU) incorporation assay and Cell Counting Kit-8. FBW7 protein expression levels were observed using western blotting. miR-223 expression was increased in the HCC cells with sorafenib resistance. HCC cells with miR-223 knockdown had significantly increased sorafenib sensitivity, but the miR-223 mimic had the opposite effect. The TargetScan web server predicted that FBW7 is a target of miR-223, which was confirmed by western blotting. Furthermore, FBW7 siRNA transfection increased HCC cell resistance to sorafenib in an obvious manner, and entirely eliminated the effect of the miR-223 inhibitor on enhancing sorafenib sensitivity. To conclude, miR-223 expression is upregulated in sorafenib-resistant HCC cells, and miR-223 knockdown significantly enhances HCC cell sensitivity to sorafenib by increasing expression of the target gene, FBW7, suggesting that miR-223 may be a new therapeutic target for overcoming sorafenib resistance.