Correction to: Forkhead box (FOX) G1 promotes hepatocellular carcinoma epithelial-Mesenchymal transition by activating Wnt signal through forming T-cell factor-4/Betacatenin/FOXG1 complex

Abstract Background Forkhead box G1 (FOXG1) is a member of the Fox transcription factor family involved in regulation of many cancers. However, the role of FOXG1 in hepatocellular carcinogenesisis largely unclear. The present study aimed at examining the biological function and underlying mechanism of FOXG1 on hepatocellular carcinoma (HCC) tumor metastasis as well as its clinical significance. Methods Levels of FOXG1 were determined by immunohistochemical and real-time PCR analysis in HCC cell lines and human HCC samples. The effect of FOXG1 on cancer cell invasion and metastasis was investigated in vitro and in vivo in either FOXG1-silenced or overexpressing human HCC cell lines. Immunoprecipitation and chromatin immunoprecipitation assays were performed to investigate the interaction of FOXG1, β-catenin, TCF4 and the effect on Wnt target-gene promoters. Results In human HCC, the level of FOXG1 progressively increased from surrounding non tumorous livers to HCC, reaching the highest levels in metastatic HCC. Furthermore, expression levels of FOXG1 directly correlated with cancer cell epithelial-mesenchymal transition (EMT) phenotype. In FOXG1-overexpressing cells, FOXG1 promotes the stabilization and nuclear accumulation of β-catenin by directly binding to β-catenin and it associates with the lymphoid enhancer factor/T cell factor proteins (LEF/TCFs) on Wnt responsive enhancers (WREs) in chromatin. Conclusions The results show that FOXG1 plays a key role in mediating cancer cell metastasis through the Wnt/β-catenin pathway in HCC cells and predicts HCC prognosis after surgery. Targeting FOXG1 may provide a new approach for therapeutic treatment in the future.

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T‑cell immunoglobulin mucin‑3 as a potential inducer of the epithelial‑mesenchymal transition in hepatocellular carcinoma

Oncology Letters ◽

10.3892/ol.2017.6961 ◽

2017 ◽

Cited By ~ 2

Author(s):

Huapeng Lin ◽

Bin Yang ◽

Mujian Teng

Keyword(s):

Hepatocellular Carcinoma ◽

T Cell ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition

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Drug Design Targeting T-Cell Factor-Driven Epithelial–Mesenchymal Transition as a Therapeutic Strategy for Colorectal Cancer

Journal of Medicinal Chemistry ◽

10.1021/acs.jmedchem.9b01065 ◽

2019 ◽

Vol 62 (22) ◽

pp. 10182-10203 ◽

Cited By ~ 3

Author(s):

Adedoyin D. Abraham ◽

Hector Esquer ◽

Qiong Zhou ◽

Nicholas Tomlinson ◽

Brayden D. Hamill ◽

...

Keyword(s):

Colorectal Cancer ◽

T Cell ◽

Drug Design ◽

Therapeutic Strategy ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

T Cell Factor

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Snail and Slug Promote Epithelial-Mesenchymal Transition through β-Catenin–T-Cell Factor-4-dependent Expression of Transforming Growth Factor-β3

Molecular Biology of the Cell ◽

10.1091/mbc.e08-05-0506 ◽

2008 ◽

Vol 19 (11) ◽

pp. 4875-4887 ◽

Cited By ~ 290

Author(s):

Damian Medici ◽

Elizabeth D. Hay ◽

Bjorn R. Olsen

Keyword(s):

T Cell ◽

Growth Factor ◽

Transforming Growth Factor ◽

Epithelial Mesenchymal Transition ◽

Signaling Mechanism ◽

Mesenchymal Transition ◽

T Cell Factor ◽

Snail Family ◽

Transcription Complexes ◽

Tgf Β1

Members of the Snail family of transcription factors have been shown to induce epithelial-mesenchymal transition (EMT), a fundamental mechanism of embryogenesis and progressive disease. Here, we show that Snail and Slug promote formation of β-catenin–T-cell factor (TCF)-4 transcription complexes that bind to the promoter of the TGF-β3 gene to increase its transcription. Subsequent transforming growth factor (TGF)-β3 signaling increases LEF-1 gene expression causing formation of β-catenin–lymphoid enhancer factor (LEF)-1 complexes that initiate EMT. TGF-β1 or TGF-β2 stimulates this signaling mechanism by up-regulating synthesis of Snail and Slug. TGF-β1- and TGF-β2-induced EMT were found to be TGF-β3 dependent, establishing essential roles for multiple TGF-β isoforms. Finally, we determined that β-catenin–LEF-1 complexes can promote EMT without upstream signaling pathways. These findings provide evidence for a unified signaling mechanism driven by convergence of multiple TGF-β and TCF signaling molecules that confers loss of cell–cell adhesion and acquisition of the mesenchymal phenotype.

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FOXO3-induced lncRNA LOC554202 contributes to hepatocellular carcinoma progression via the miR-485-5p/BSG axis

Cancer Gene Therapy ◽

10.1038/s41417-021-00312-w ◽

2021 ◽

Author(s):

Lin Yang ◽

Wan-li Deng ◽

Bao-guo Zhao ◽

Yao Xu ◽

Xiao-wen Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Diagnostic Value ◽

Clinical Prognosis ◽

Mesenchymal Transition ◽

Beneficial Effects ◽

Forkhead Box ◽

Advanced Stages ◽

And Function ◽

Poor Clinical Prognosis

AbstractLong non-coding RNAs (LncRNAs) have played very important roles in the malignancy behaviors of hepatocellular carcinoma (HCC). LncRNA LOC554202 (LOC554202) was a newly identified tumor-related lncRNA. However, its expression and function in HCC remained unknown. In this study, we firstly reported that LOC554202 expression was distinctly upregulated in HCC specimens and cell lines. Clinical assays indicated that increased LOC554202 expression had a diagnostic value for HCC patients and was positively associated with advanced stages and poor clinical prognosis. Additionally, forkhead box O3(FOXO3) could bind directly to the LOC554202 promoter region and activate its transcription. Functionally, we observed that knockdown of LOC554202 suppressed the proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) progress of HCC cells, and promoted apoptosis. Mechanistically, LOC554202 competitively bound to miR-485-5p and prevented the suppressive effects of miR-485-5p on its target gene basigin (BSG), which finally led to HCC metastasis, EMT, and docetaxel chemoresistance. Our data demonstrated that FOXO3-induced LOC554202 contributed to HCC progression by upregulating BSG via competitively binding to miR-485-5p, which suggested that the regulation of the FOXO3/LOC554202/miR-485-5p/BSG axis may have beneficial effects in the treatment of HCC.

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FOXK2 downregulation suppresses EMT in hepatocellular carcinoma

Open Medicine ◽

10.1515/med-2020-0129 ◽

2020 ◽

Vol 15 (1) ◽

pp. 702-708

Author(s):

Jian Kong ◽

Qingyun Zhang ◽

Xuefeng Liang ◽

Wenbing Sun

Keyword(s):

Hepatocellular Carcinoma ◽

Colony Formation ◽

Epithelial Mesenchymal Transition ◽

Akt Signaling ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Endogenous Expression ◽

Forkhead Box ◽

Binding Factor ◽

E Cadherin

AbstractForkhead box K2 (FOXK2) was first identified as an NFAT-like interleukin-binding factor. FOXK2 has been reported to act as either oncogene or tumor suppressor. However, functional and regulating mechanisms of FOXK2 in epithelial–mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) remain unclear. An FOXK2-specific siRNA was employed to decrease the endogenous expression of FOXK2. MTT assay, colony formation and transwell assay were used to evaluate proliferation, migration and invasion of Hep3B and HCCLM3 cells, respectively. The protein expression associated with EMT and Akt signaling pathways was evaluated using western blot. FOXK2 downregulation could inhibit cell proliferation and colony formation and suppress migration and invasion in Hep3B and HCCLM3 cells. The expression of E-cadherin was significantly upregulated, and the expression of snail and p-Akt was significantly downregulated in siFOXK2-transfected cells compared with control cells. SF1670 induced the expression of p-Akt and snail and suppressed the expression of E-cadherin in Hep3B and HCCLM3 cells. SF1670 promoted the invasion and colony formation of Hep3B and HCCLM3 cells. SF1670 partly inhibited the effect of FOXK2 suppression on Hep3B and HCCLM3 cells. In conclusion, this study revealed that FOXK2 downregulation suppressed the EMT in HCC partly through inhibition of the Akt signaling pathway.

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TNF-α induces epithelial-mesenchymal transition through NF-κB in hepatocellular carcinoma

Academic Journal of Second Military Medical University ◽

10.3724/sp.j.1008.2013.00271 ◽

2013 ◽

Vol 33 (3) ◽

pp. 271-276

Author(s):

Xing-rui KOU ◽

Ying-ying JING ◽

Guo-feng YU ◽

Meng-chao WU ◽

Li-xin WEI

Keyword(s):

Hepatocellular Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Tnf Α

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Intergrated Analysis of ELMO1, Serves As a Link between Tumor Mutation Burden and Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma

SSRN Electronic Journal ◽

10.2139/ssrn.3350534 ◽

2019 ◽

Author(s):

Hong Peng ◽

Yi Zhang ◽

Zhiwei Zhou ◽

Yu Guo ◽

Xiaohui Huang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Tumor Mutation Burden ◽

Mesenchymal Transition ◽

Mutation Burden

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MYC-targeted WDR4 promotes proliferation, metastasis, and sorafenib resistance by inducing CCNB1 translation in hepatocellular carcinoma

Cell Death and Disease ◽

10.1038/s41419-021-03973-5 ◽

2021 ◽

Vol 12 (7) ◽

Author(s):

Peng Xia ◽

Hao Zhang ◽

Kequan Xu ◽

Xiang Jiang ◽

Meng Gao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Epithelial Mesenchymal Transition ◽

P53 Protein ◽

Rna Modifications ◽

M Cell ◽

Mesenchymal Transition ◽

Akt Phosphorylation ◽

Repeat Domain ◽

Cell Cycle Transition

AbstractHepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, there still remains a lack of effective diagnostic and therapeutic targets for this disease. Increasing evidence demonstrates that RNA modifications play an important role in the progression of HCC, but the role of the N7-methylguanosine (m7G) methylation modification in HCC has not been properly evaluated. Thus, the goal of the present study was to investigate the function and mechanism of the m7G methyltransferase WD repeat domain 4 (WDR4) in HCC as well as its clinical relevance and potential value. We first verified the high expression of WDR4 in HCC and observed that upregulated WDR4 expression increased the m7G methylation level in HCC. WDR4 promoted HCC cell proliferation by inducing the G2/M cell cycle transition and inhibiting apoptosis in addition to enhancing metastasis and sorafenib resistance through epithelial-mesenchymal transition (EMT). Furthermore, we observed that c-MYC (MYC) can activate WDR4 transcription and that WDR4 promotes CCNB1 mRNA stability and translation to enhance HCC progression. Mechanistically, we determined that WDR4 enhances CCNB1 translation by promoting the binding of EIF2A to CCNB1 mRNA. Furthermore, CCNB1 was observed to promote PI3K and AKT phosphorylation in HCC and reduce P53 protein expression by promoting P53 ubiquitination. In summary, we elucidated the MYC/WDR4/CCNB1 signalling pathway and its impact on PI3K/AKT and P53. Furthermore, the result showed that the m7G methyltransferase WDR4 is a tumour promoter in the development and progression of HCC and may act as a candidate therapeutic target in HCC treatment.

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