Elevated FOXC2 Expression Promotes Invasion of HCC Cell Lines and is Associated with Poor Prognosis in Hepatocellular Carcinoma

Yang, Fang; Liu, Lizhi; Zhang, Kun; Cai, Qiucheng; Liu, Jianyong; Jiang, Yi

doi:10.1159/000484586

Cited by 12 publications

(15 citation statements)

References 22 publications

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“…PRMT1 inhibition may be an effective therapeutic strategy for overcoming intrinsic cetuximab resistance in triple-negative breast cancer. In human melanoma, Li, et al reported that PRMT1 is overexpressed in human melanoma and may regulate tumour growth and metastasis via targeting ALCAM [8]. Eberhardt, et al indicated that PRMT1 is a novel regulator of MYCN, which implicates PRMT1 as a potential therapeutic target in neuroblastoma pathogenesis [28].…”

Section: Discussionmentioning

confidence: 99%

“…However, HCC patients cannot be totally cured due to prognosis difficulty, recurrence and early blood vessel invasion [2][3][4][5]. These problems cannot be solved because fundamental studies have not fully clarified the molecular mechanisms of HCC [6][7][8]. Therefore, it is important to fully understand HCC development and find new molecular targets for HCC treatment.…”

Section: Introductionmentioning

confidence: 99%

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PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway

Zhang

Jiang

Zhong

et al. 2018

Cell Physiol Biochem

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Background/Aims: Although it has been widely accepted that protein arginine methyltransferase 1 (PRMT1) is a cancer-promoting gene in various cancers, the mechanism of PRMT1 in hepatocellular carcinoma (HCC) requires more exploration. This study aimed to investigate the role of PRMT1 in HCC growth and metastasis. Methods: We compared PRMT1 expression and clinicopathological characteristics using paired HCC and adjacent noncancerous liver tissues from 210 patients and immunohistochemistry analyses. Cell proliferation, colony formation and migration were determined in HCC cell lines with PRMT1 overexpression or downregulation through MTT, crystal violet and Boyden chamber assays. Tumour growth was monitored in a xenograft model, and intrahepatic metastasis models were established. Results: PRMT1 expression was greatly increased in clinical HCC samples and strongly associated with poor prognosis and recurrence; PRMT1 expression was also positively correlated with microvascular invasion (P = 0.024), tumour differentiation (P = 0.014), tumour size (P = 0.002), and portal vein tumour thrombus (PVTT) (P = 0.028). Cell proliferation, colony formation and migration in vitro were enhanced by PRMT1 upregulation and decreased by PRMT1 downregulation in HCC cell lines. Moreover, low PRMT1 expression resulted in slow tumour growth and decreased tumour weight in vivo, as well as tumour metastasis. These phenotypes were associated with STAT3 signalling pathway activation. Cryptotanshinone, a STAT3 inhibitor, inhibited STAT3 phosphorylation and reversed the HCC phenotype of PRMT1 expression. Conclusions: We revealed a significant role for PRMT1 in HCC progression and metastasis in vitro and in vivo via STAT3 signalling pathway activation. PRMT1 may be a potential novel prognostic biomarker and new therapeutic target for HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway

Zhang

Jiang

Zhong

et al. 2018

Cell Physiol Biochem

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“…These data were consistent with other cancers, including breast, colorectal, nasopharyngeal, esophageal, lung, ovarian, cholangiocarcinoma, and osteosarcoma [ 11 – 17 ]. Yang et al have shown that the up-regulation of FOXC2 is associated with tumor size, vascular invasion, advanced TNM stage, promoting proliferation, and invasion in HCC [ 18 ]. However, few studies have examined the expressional relationship of FOXC2 and other EMT-related genes in HCC.…”

Section: Introductionmentioning

confidence: 99%

High expression of forkhead box protein C2 is associated with aggressive phenotypes and poor prognosis in clinical hepatocellular carcinoma

et al. 2018

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BackgroundHepatocellular carcinoma (HCC) is one of the major causes of tumor death; thus, the identification of markers related to its diagnosis and prognosis is critical. Previous studies have revealed that epithelial-to-mesenchymal transition (EMT) is involved in tumor invasion and metastasis, and the forkhead box protein C2 (FOXC2) has been shown to promote tumor cell proliferation, invasion, and EMT. In the present study, we examined the clinicopathological significance of FOXC2 and EMT-related markers in clinical HCC specimens and identified factors related to the diagnosis and prognosis of HCC.MethodsThe expression of FOXC2 and EMT-related markers was evaluated by immunohistochemistry in 84 cases of hepatocellular carcinoma.ResultsA high expression of FOXC2 was observed in 26 of 84 cases, and expression was significantly correlated with background liver cirrhosis, poor tumor differentiation, high serum AFP, and elevated cell proliferation markers. In addition, this high expression was related to the induction of the Cadherin switch and vimentin expression and was an independent predictor for poor prognosis.ConclusionThe high expression of FOXC2 in HCC is correlated with tumor malignancy and poor prognosis, suggesting that FOXC2 may be an important prognostic factor for HCC.

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“…A previous report shows that FOXC2 over‐expression can promote breast cancer cells invasion and metastasis in rats (Mani et al, ). Moreover, it has been proved that FOXC2 silencing markedly represses the migration and invasion of hepatoma cells (Yang et al, ). Nevertheless, the roles of FOXC2 on trophoblast cells are still unclear.…”

Section: Discussionmentioning

confidence: 99%

Forkhead box C2 promotes the invasion ability of human trophoblast cells through Hedgehog (Hh) signaling pathway

Zhang

2018

Cell Biology International

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Embryonic development depends on the normal invasion of trophoblast cells. Forkhead box C2 (FOXC2) is a member of Forkhead box family, which is involved in the tumor cells invasion. The aim of this study was to explore the roles of FOXC2 on the invasion of human trophoblast cells, and further study its molecular mechanism. The mRNA and protein levels of FOXC2 in human normal trophoblast and choriocarcinoma cell lines were analyzed by quantitative real-time PCR (qRT-PCR) and Western blot assays, respectively. Methylthiazolyldiphenyl-tetrazo lium bromide (MTT) and transwell assays were separately performed to detect the adhesion and invasion of normal trophoblast cells treated with exogenous FOXC2 and FOXC2 siRNA. QRT-PCR and Western blot assays were used to test levels of the epithelial-mesenchymal transition (EMT)-related and Hedgehog (Hh) signaling pathway-related factors, respectively. Herein, our results found that the expression levels of FOXC2 in normal trophoblast cells were lower than choriocarcinoma cells. FOXC2 over-expression remarkably strengthened the adhesion and invasion abilities of normal trophoblast cells. Moreover, over-expression of FOXC2 significantly promoted the expression of human leukocyte antigen-G (HLA-G), matrix metalloproteinase-2 (MMP-2), Vimentin, sonic hedgehog (Shh), Glioma-associated oncogene homolog 1 (Gli1), and Snail, and inhibited E-cadherin expression. However, it showed the opposite tendency in FOXC2 siRNA group. In addition, there was no significant change in the expression of MMP9 among different groups. Above results illustrated that FOXC2 could promote the invasion ability of normal trophoblast cells by EMT-mediated Hh pathway.

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Elevated FOXC2 Expression Promotes Invasion of HCC Cell Lines and is Associated with Poor Prognosis in Hepatocellular Carcinoma

Cited by 12 publications

References 22 publications

PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway

PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway

High expression of forkhead box protein C2 is associated with aggressive phenotypes and poor prognosis in clinical hepatocellular carcinoma

Forkhead box C2 promotes the invasion ability of human trophoblast cells through Hedgehog (Hh) signaling pathway

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