Chen Jinzhang, Rong Xiaoxiang, Liu Xinhui, Zheng Dayong, Rong Xiaodong, Chen Fengsheng, Zhao Peng, Liu Feiye, Ruan Jian
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Hepatology Unit and Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510000 People's Republic of China.
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510000 Guangdong People's Republic of China.
Cancer Cell Int. 2020 May 26;20:196. doi: 10.1186/s12935-020-01265-0. eCollection 2020.
Forkhead box C2 (FOXC2) is a crucial factor involving in various cancers. However, its functions in hepatocellular carcinoma (HCC) is unknown. Here, we explored the role of FOXC2 in the progression of HCC and its potential mechanisms.
FOXC2 expression in HCC tissue and cells were detected by immunohistochemistry or western blot and real-time PCR. CCK8, wound healing and transwell assay were used to measure cell growth and invasion. Tumor formation experiment was carried out to assess the tumorigenicity of HCC cells. Regulation of FOXC2 on Ang-2 was validated by luciferase assay and complementary experiments.
Increased FOXC2 expression was found to be associated positively with more aggressive clinicopathologic features. HCC patients with higher FOXC2 expression had significantly shorter overall survival. FOXC2 expression was indentified as an independent risk factor for resectable HCC. Increased FOXC2 expression accelerated the migration and invasion of HCC cells, accompanied by enhanced Ang-2 expression. Likewise, FOXC2 knockdown yielded opposite results. Moreover, FOXC2 stimulated the activation of the Ang-2 promoter. Suppression of Ang-2 expression hindered the FOXC2-mediated EMT processs, cell migration and invasion of HCC.
FOXC2 is a novel prognostic predictor for HCC and may facilitate the growth and invasion through Ang-2.
叉头框C2（FOXC2）是参与多种癌症的关键因素。然而，其在肝细胞癌（HCC）中的作用尚不清楚。在此，我们探讨了FOXC2在HCC进展中的作用及其潜在机制。
通过免疫组织化学、蛋白质免疫印迹法和实时聚合酶链反应检测HCC组织和细胞中FOXC2的表达。采用细胞计数试剂盒8法、伤口愈合实验和Transwell实验检测细胞生长和侵袭能力。进行肿瘤形成实验以评估HCC细胞的致瘤性。通过荧光素酶报告基因检测和补充实验验证FOXC2对血管生成素2（Ang-2）的调控作用。
发现FOXC2表达增加与更具侵袭性的临床病理特征呈正相关。FOXC2表达较高的HCC患者总生存期明显较短。FOXC2表达被确定为可切除HCC的独立危险因素。FOXC2表达增加加速了HCC细胞的迁移和侵袭，同时伴有Ang-2表达增强。同样，敲低FOXC2则产生相反的结果。此外，FOXC2刺激了Ang-2启动子的激活。抑制Ang-2表达可阻碍FOXC2介导的上皮-间质转化过程、HCC细胞的迁移和侵袭。
FOXC2是一种新的HCC预后预测指标，可能通过Ang-2促进HCC的生长和侵袭。
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