FBXO17 promotes malignant progression of hepatocellular carcinoma by activating wnt/β-catenin pathway

This study was to investigate the expression of FBXO17 in hepatocellular carcinoma (HCC) and its relationship with clinical HCC features and patient prognosis.

The expression of FBXO17 at mRNA level and protein level in tumor tissues and paracancerous tissues of 45 patients with HCC was respectively detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. Besides, FBXO17 expression and its pathological characteristics of HCC, as well as the prognosis of patients, were also analyzed. Then, the expression level of FBXO17 in HCC cell lines was further verified using qRT-PCR assay. In addition, FBXO17 overexpression and knockdown models were constructed using lentivirus in HCC cell lines including Bel-7402 and HepG2. Cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EDU), cell clone experiment, flow cytometry, and transwell assay were used to explore the effect of FBXO17 on the biological function of HCC cells. Finally, whether FBXO17 could exert its biological characteristics through wnt/β-catenin pathway was determined.

Results showed that FBXO17 expression in tumor tissues of HCC patients was markedly higher than that in adjacent tissues. Meanwhile, compared with patients with low FBXO17 expression, the pathological grade was higher and the overall survival rate was lower in patients with high expressed FBXO17. In vitro experiments showed that the cell proliferation and metastasis ability in the Anti-FBXO17 group was markedly decreased, and the apoptosis was significantly enhanced compared with the NC group. In contrast, overexpression of FBXO17 markedly increased cell proliferation and metastasis ability while decreased cell apoptosis. Finally, Western blot results indicated that silencing FBXO17 might function through downregulating the expression of proteins in wnt/β-catenin pathway such as c-Myc, MMP-9, and MMP-2 while upregulating GSK-3β level, thereby promoting the malignant progression of HCC.

FBXO17 was significantly increased in tumor tissues of HCC patients, which was significantly associated with pathological stage and poor prognosis of these patients. In addition, FBXO17 might promote the malignant progression of HCC by inhibiting wnt/β-catenin pathway.