Abstract
BackgroundForkhead 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.MethodsFOXC2 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.ResultsIncreased 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.ConclusionsFOXC2 is a novel prognostic predictor for HCC and may facilitate the growth and invasion through Ang-2.
Highlights
Forkhead box C2 (FOXC2) is a crucial factor involving in various cancers
FOXC2 expression in hepatocellular carcinoma tissues 280 paraffin-embedded HCC samples and 40 normal samples were immunohistochemically analyzed for FOXC2 expression
HCC cases were divided into two groups according to the extent and intensity of FOXC2 staining: the low FOXC2 expression group (FOXC2-Lo) and the high FOXC2 expression group (FOXC2-Hi)
Summary
Forkhead box C2 (FOXC2) is a crucial factor involving in various cancers. Before the operation on the patients, poor prognosis occurs due to several clinicopathological features (e.g., Chen et al Cancer Cell Int (2020) 20:196 large tumor size, poorly differentiated phenotype, poorly differentiated phenotype, and portal venous invasion), the molecular mechanisms guiding the development and pathogenesis of HCC remain to be elucidated. FOXC2 may have a crucial role in the drug-resistant cancer phenotypes, like that of ovarian cancer, nasopharyngeal carcinoma, breast cancer, and osteosarcoma [13,14,15,16]. Enhanced expression of FOXC2 has been observed in the HCC tissues and relates inversely with patient survival [17], but data regarding the underlying role of FOXC2 in HCC development and progression are limited
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