Hu Yabing, Huang Yongchu, Xie Xiaohang, Li Longshan, Zhang Yong, Zhang Xiaochao
Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Laboratory Medicine, Wuhan No.1 Hospital, Wuhan, China.
Cancer Cell Int. 2023 Sep 16;23(1):205. doi: 10.1186/s12935-023-03053-y.
Hepatocellular 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.
Immunohistochemistry 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.
ARF6 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.
Our 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.
肝细胞癌（HCC）在全球癌症中具有高死亡率。然而，HCC增殖的具体机制仍不清楚。在本研究中，我们表明ARF6的高表达与不良临床预后相关，这可能促进HCC的增殖。
采用免疫组织化学和蛋白质印迹法检测HCC组织中ARF6的表达水平。我们分析了ARF6在原发性HCC患者中的临床意义。我们通过体外CCK8、集落形成试验和体内裸鼠异种移植模型评估ARF6对肿瘤增殖的影响。进行免疫荧光以研究ARF6的定位。使用蛋白质印迹法检测细胞周期相关蛋白。此外，我们通过蛋白质印迹法、免疫组织化学和异种移植试验检测HCC中ARF6与STAT3信号传导之间的相关性。
与相邻正常肝组织相比，HCC组织中ARF6上调。ARF6表达增加与肿瘤分化差、肿瘤包膜不完整、肿瘤TNM分期高和预后不良相关。ARF6明显促进HCC细胞增殖、集落形成和细胞周期进程。体内裸鼠异种移植模型显示ARF6促进肿瘤生长。此外，ARF6激活STAT3信号传导，并且ARF6表达与HCC组织中磷酸化STAT3水平呈正相关。此外，在STAT3干预后，ARF6对肿瘤促进的作用减弱，这表明ARF6在HCC中通过STAT3信号传导发挥作用。
我们的结果表明，ARF6通过激活STAT3信号传导促进HCC增殖，提示ARF6可能作为HCC患者潜在的预后和治疗靶点。
