FOX transcription factor family in hepatocellular carcinoma

Gong, Zhongqin; Yu, Jianqing; Yang, Shengsheng; Lai, Paul B.S.; Chen, George G

doi:10.1016/j.bbcan.2020.188376

Cited by 31 publications

(20 citation statements)

References 127 publications

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“…Studies have shown that FOXA2 plays a key role in the pathogenesis and occurrence of HCC (Lee et al, 2005). In addition to its pro-differentiation factor role in liver development, functionally, FOXA2 has been considered as a transcriptional suppressor of epithelial to mesenchymal transition (EMT) process and has been documented to suppress carcinogenesis in HCC (Gong et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

O‐GlcNAcylation promotes the migratory ability of hepatocellular carcinoma cells via regulating FOXA2 stability and transcriptional activity

Huang

Guo

et al. 2021

Journal Cellular Physiology

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O-GlcNAcylation is a posttranslational modification that regulates numerous nuclear and cytoplasmic proteins and is emerging as a key regulator of various biological processes, such as transcription, signal transduction, and cell motility.Although increasing evidence has shown that elevated levels of global O-GlcNAcylation are linked to the metastasis in hepatocellular carcinoma (HCC) cells, the underlying mechanism is still ambiguous. In this study, we demonstrated that forkhead box protein A2 (FOXA2), an essential transcription factor for liver homeostasis and HCC developing, was O-GlcNAcylated by O-GlcNAc transferase (OGT) and regulates HCC cells migration and invasion. Opposite FOXA2 and OGT expression tendency were observed in HCC tissues, and lower FOXA2 levels predicted a poor prognosis in HCC patients. The reduction of FOXA2 in HCC cells was found to be inversely correlated with the cellular O-GlcNAcylation and cell migratory ability. Notably, we found that FOXA2 was modified by O-GlcNAcylation and that O-GlcNAcylation activated the ubiquitination degradation of FOXA2 in highly metastatic HCC cells. Although this modification did not affect FOXA2 nuclear localization capability, O-GlcNAcylation on FOXA2 was key for attenuating FOXA2-mediated transcription. O-GlcNAcylation decreased the transcription of FOXA2 downstream target gene E-cadherin and it ultimately promoted O-GlcNAcylation-mediated HCC cell migration and invasion. The results provide insights into the role of O-GlcNAcylation in regulating FOXA2 activity and suggest its important implications in HCC metastasis.

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Section: Introductionmentioning

confidence: 99%

O‐GlcNAcylation promotes the migratory ability of hepatocellular carcinoma cells via regulating FOXA2 stability and transcriptional activity

Huang

Guo

et al. 2021

Journal Cellular Physiology

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“…Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality, and up to 600000 people die from this disease worldwide every year [ 1 , 2 ]. Recently, some significant improvements have been achieved in clinical diagnosis and treatment.…”

Section: Introductionmentioning

confidence: 99%

MiR-466 Inhibits the Progression of Severe Hepatocellular Carcinoma via Regulating FMNL2-Mediated Activation of NF-κB and Wnt/β-Catenin Pathways

2021

Journal of Oncology

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Hepatocellular carcinoma (HCC) has threatened the health of humans, and some evidence has indicated that miR-466 involves the progressions of some cancers. This study focused on the role of miR-466 in the formation and development of HCC. The expression levels of miR-466 in the tissues of patients and HCC cell lines were measured by qRT-PCR, and CCK-8, transwell assay, and flow cytometry assay were used to observe the functions of miR-466 on the HCC cells. Moreover, the miRNA databases, dual-luciferase reporter assay, and Western blot were used for the investigation of the regulation mechanism of miR-466 on HCC cells. The results showed that miR-466 was significantly downregulated in HCC tissues and cell lines, and inhibited proliferation, invasion, and high apoptosis were found in HCC cells when miR-466 was overexpressed. The results confirmed that FMNL2 was a target of miR-466, and increased FMNL2 could reverse the effects of miR-466 on the phenotype of HCC cells. Besides, it was also found that miR-466 was involved in the regulation of NF-κB and Wnt/β-catenin pathways in HCC cells via targeting FMNL2. In conclusion, the results of this study suggest that miR-466 regulates the activities of NF-κB and Wnt/β-catenin pathways to inhibit the progression of HCC cells via targeting FMNL2.

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“…As a core member of the human FOX gene family, FOXD1 expression may be an oncogene involving cancer progression and has been critically participated in cell migration and apoptosis, cancer stem cell self-renewal as well as other physiological and pathological processes [ 16 – 18 ]. Previous studies have shown that FOXD1 may be an oncogene related to tumor development and act as a potential diagnostic biomarker and anti-cancer therapeutic target [ 9 , 11 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

Aberrant overexpression of transcription factor Forkhead box D1 predicts poor prognosis and promotes cancer progression in HNSCC

Yan

et al. 2021

BMC Cancer

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Objectives Forkhead box D1, the core transcription factor member of FOX family, has gradually seen as a key cancerous regulatory. However, its expression and carcinogenicity in head and neck squamous cell carcinoma (HNSCC) have not been reported yet. This study was to investigate its expression pattern, clinicopathological significance and biological roles in HNSCC. Methods HNSCC data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was used to indicate the detailed expression pattern and outcome association of FOXD1, while Western Blot assay to detect FOXD1 level in a panel of HNSCC cell lines as well as immunocytochemistry to explore FOXD1 protein abundance and sublocation. Series of siRNA-mediated FOXD1 knock-down experiments to assess the proliferation, migration, invasion and anti- apoptosis ability after FOXD1 down-regulation. Bioinformatic analysis to find out which biological function and cancer-related pathways of FOXD1 associated genes involved in. Results FOXD1 mRNA was significantly overexpressed in TCGA-HNSCC, GSE6631, GSE12452, GSE25099 and GSE30784. Besides, IHC results shown that nuclear location FOXD1 protein was significantly higher in primary HNSCC specimens from cohort involved in this study. Also, FOXD1 abundance was significantly correlated with cervical node metastasis and poor over-all/disease-free survival after combination analysis with patient pathological information. siRNA-mediated FOXD1 knock-down significantly inhibited cell proliferation, migration and invasion and induced apoptosis in HNSCC cells. Further analysis of GSEA, GO and KEGG showed that FOXD1 expression was significantly associated with oncological function and cancer-related pathways. Conclusions Taken together, our study implies that the potential oncogene, FOXD1, facilitates oncological behavior who can be identified as a brand-new HNSCC biomarker with diagnostic and prognostic significance.

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FOX transcription factor family in hepatocellular carcinoma

Cited by 31 publications

References 127 publications

O‐GlcNAcylation promotes the migratory ability of hepatocellular carcinoma cells via regulating FOXA2 stability and transcriptional activity

O‐GlcNAcylation promotes the migratory ability of hepatocellular carcinoma cells via regulating FOXA2 stability and transcriptional activity

MiR-466 Inhibits the Progression of Severe Hepatocellular Carcinoma via Regulating FMNL2-Mediated Activation of NF-κB and Wnt/β-Catenin Pathways

Aberrant overexpression of transcription factor Forkhead box D1 predicts poor prognosis and promotes cancer progression in HNSCC

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