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

Tang,Xiaofeng; Yang,Weigang; Shu,Zheyue; Shen,Xiaodong; Zhang,Weichen; Cen,Chao; Cao,Linping; Zhang,Min; Zheng,Shusen; Yu,Jun

doi:10.3892/or.2018.6908

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

Authors:
- Xiaofeng Tang
- Weigang Yang
- Zheyue Shu
- Xiaodong Shen
- Weichen Zhang
- Chao Cen
- Linping Cao
- Min Zhang
- Shusen Zheng
- Jun Yu
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Affiliations: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
Published online on: December 6, 2018 https://doi.org/10.3892/or.2018.6908
Pages: 1231-1237

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Abstract

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.

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