Journal
CANCER CELL INTERNATIONAL
Volume 23, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12935-023-03053-y
Keywords
Hepatocellular carcinoma; ARF6; STAT3; Proliferation; Therapy
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In this study, we found that high expression of ARF6 is associated with poor prognosis and promotes the proliferation of hepatocellular carcinoma (HCC). ARF6 was upregulated in HCC tissues and correlated with poor tumor differentiation, incomplete tumor encapsulation, advanced tumor TNM stage, and poor prognosis. ARF6 activated the STAT3 signaling pathway to enhance HCC cell proliferation and tumor growth. These findings suggest that ARF6 may serve as a potential prognostic and therapeutic target for HCC patients.
BackgroundHepatocellular Carcinoma (HCC) possesses the high mortality in cancers worldwide. Nevertheless, the concrete mechanism underlying HCC proliferation remains obscure. In this study, we show that high expression of ARF6 is associated with a poor clinical prognosis, which could boost the proliferation of HCC.MethodsImmunohistochemistry and western blotting were used to detect the expression level of ARF6 in HCC tissues. We analyzed the clinical significance of ARF6 in primary HCC patients. We estimated the effect of ARF6 on tumor proliferation with in vitro CCK8, colony formation assay, and in vivo nude mouse xenograft models. Immunofluorescence was conducted to investigate the ARF6 localization. western blotting was used to detect the cell cycle-related proteins with. Additionally, we examined the correlation between ARF6 and STAT3 signaling in HCC with western blotting, immunohistochemistry and xenograft assay.ResultsARF6 was upregulated in HCC tissues compared to adjacent normal liver tissues. The increased expression of ARF6 correlated with poor tumor differentiation, incomplete tumor encapsulation, advanced tumor TNM stage and poor prognosis. ARF6 obviously promoted HCC cell proliferation, colony formation, and cell cycle progression. In vivo nude mouse xenograft models showed that ARF6 enhanced tumor growth. Furthermore, ARF6 activated the STAT3 signaling and ARF6 expression was positively correlated with phosphorylated STAT3 level in HCC tissues. Furthermore, after intervening of STAT3, the effect of ARF6 on tumor-promoting was weakened, which demonstrated ARF6 functioned through STAT3 signaling in HCC.ConclusionsOur results indicate that ARF6 promotes HCC proliferation through activating STAT3 signaling, suggesting that ARF6 may serve as potential prognostic and therapeutic targets for HCC patients.
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