RETRACTED ARTICLE: Forkhead box (FOX) G1 promotes hepatocellular carcinoma epithelial-Mesenchymal transition by activating Wnt signal through forming T-cell factor-4/Beta-catenin/FOXG1 complex

Zheng, Xingrong; Lin, Jiaxin; Wu, Hewei; Mo, Zhishuo; Lian, Yunwen; Wang, Peipei; Hu, Zhaoxia; Gao, Zhiliang; Peng, Liang; Xie, Chan

doi:10.1186/s13046-019-1433-3

Cited by 30 publications

(25 citation statements)

References 36 publications

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“…However, a few genes showed opposite expression trend, such as Cyp1b1 and HLA-DPA1, which increased in BM1/BM2 cells while decreased in B02 cells [20]. Although Cyp1b1 has been reported to promote breast cancer metastasis [22], more functional validation both in vitro and in vivo is still required. Additional genes, such as Foxg1, Trem1, Slpi, et al, were only identified by our current study with upregulation in the bone-metastatic breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Cancer stem cell property and gene signature in bone-metastatic Breast Cancer cells

Luo¹,

Xu²,

Li³

et al. 2020

Int. J. Biol. Sci.

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The majority of the deaths from breast cancer is due to metastasis. Bone is the most common organ to which breast cancer cells metastasize. The mechanism regulating the bone-metastatic preference remains unclear; there is a lack of a gene signature to distinguish bone-metastatic breast cancer cells. Herein, florescence-labeled MDA-MB-231 cells were transplanted into the fat pads of of the mammary gland in nude mice to generate breast tumors. Tumor cells invaded into the circulation were tracked by in vivo flow cytometry system. Metastatic tumor cells in the bone were isolated using fluorescent-activated cell sorting technique, followed by assays of cell colony formation, migration and invasion, mammosphere formation in vitro, mammary gland tumorigenesis in vivo, and Next-Generation Sequencing analysis as well. Through tumor regeneration and cell sorting, two bone-metastatic cell sublines were derived from MDA-MB-231 cells; which showed higher abilities to proliferate, migrate, invade and epithelial-to-mesenchymal transit in vitro, and stronger ability to regenerate tumors and metastasize to the bone in vivo. Both cell sublines exhibited cancer stem cell-like characteristics including higher expression levels of stem cell markers and stronger ability for mommaspheres formation. Furthermore, a Normal Distribution-like pattern of the bone-metastatic cells invading into circulation was firstly identified. Deep-sequencing analysis indicated upregulation of multiple signaling pathways in regulating EMT, cell membrane budding and morphologic change, lipid metabolism, and protein translation, which are required to provide adequate metabolic enzymes, structural proteins, and energy for the cells undergoing metastasis. In conclusion, we established two bone-metastatic breast cancer cell sublines, carrying higher degree of stemness and malignancy. The gene signature distinguishing the bone-metastatic breast cancer cells holds therapeutic potentials in prevention of breast cancer metastasis to the bone.

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Section: Discussionmentioning

confidence: 99%

Cancer stem cell property and gene signature in bone-metastatic Breast Cancer cells

Luo¹,

Xu²,

Li³

et al. 2020

Int. J. Biol. Sci.

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“…Some members of the FOX family function in induction of the EMT [46]. For example, FOXD4 binds to the SNAIL3 promoter to support colorectal cancer metastasis [47], and FOXG1 mediates liver cancer metastasis through the Wnt/β-catenin pathway [48]. Snail, an Ecadherin transcription inhibitor, is a transcription target of FoxC1.…”

Section: Discussionmentioning

confidence: 99%

For COPD, regulation of miR-515-5p by hsa_circ_0061052, acting via the FoxC1/Snail pathway, is involved in cigarette smoke-induced airway remodeling

Liu

et al. 2020

Preprint

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BackgroundRegulatory networks involving non-coding RNA (ncRNA) are involved in various lung diseases. The function of circular RNA (circRNA), a recently recognized type of ncRNA, in chronic obstructive pulmonary disease (COPD), has not been elucidated.MethodsWestern blots and cellular immunofluorescence are used to check molecular biological changes and molecular interactions in cells, bioinformatics tools and luciferase reporter genes are used to assess molecular binding relationships, immunohistochemical examination of mouse lung tissue-related proteins A mouse model of COPD was used to validate related concubine mechanisms.ResultsIn the present study, we aimed to determine whether hsa_circ_0061052 participates in the EMT of HBE cells and to elucidate its biological mechanism. Experiments with cultured cells and animals showed that exposure to cigarette smoke extract (CSE) or cigarette smoke (CS) induced the EMT and led to lung dysfunction and airway remodeling. For HBE cells and the lung tissues of CS-exposed mice, the expression of hsa_circ_0061052 was elevated. To verify the function of this circRNA, knocking it out in HBE cells reversed the CSE-induced EMT. We analyzed the regulatory relationship between hsa_circ_0061052 and miR-515-5p using bioinformatics, a luciferase reporter gene, and qRT-PCR. We found that hsa_circ_0061052 was mainly distributed in the cytoplasm and acted as a sponge for miR-515-5p. Assays with a luciferase reporter gene showed that miR-515-5p binds to the 3'UTR region of FoxC1 mRNA to inhibit its transcription. For HBE cells, overexpression of miR-515-5p reversed the CSE-induced EMT. In addition, hsa_circ_0061052 regulated the expression of FoxC1/Snail by competitively binding to miR-515-5p. When an hsa_circ_0061052 siRNA and an miR-515-5p inhibitor were co-transfected into HBE cells, the effect of hsa_circ_0061052 siRNA in reducing the EMT was reversed by the inhibitor; in animal models, this effect was also evident.ConclusionExperiments relating to the mechanisms of COPD airway remodeling due to the hsa_circ_0061052/miR-515-5p/FoxC1/Snail axis point to a biomarker for COPD and provide a basis for clinical application.

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“…FOXG1 is well-known as an etiological factor in certain neurological disorders and plays a role in the epithelial-mesenchymal transition of CRC cells (a key hallmark of cancer progression), and is known to be overexpressed in CRC patients [49]. It is a nodal gene, with connections to oncogenic pathways like WNT pathway in hepatocellular carcinoma [50] and TGF-β pathway in ovarian cancer [51]. Interestingly, FOXG1 was found to be a hypermethylated stage-II salient gene.…”

Section: Discussionmentioning

confidence: 99%

Stage-differentiated modelling of methylation patterns uncovers salient biomarkers and prognostic signatures in colorectal cancer progression

Raghavendran¹,

Muthamilselvan²,

Palaniappan³

2020

Preprint

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Background: Aberrant methylation of DNA acts epigenetically to skew the gene transcription rate up or down. In this study, we have developed a comprehensive computational framework for the stage-specific analysis of methylation patterns in colorectal cancer. Methods: Combining public-domain methylation and clinical data from TCGA, the methylation β-matrix was converted into M-value matrix, annotated with sample stages and analysed for stage-specific genes using multiple approaches involving stage-differentiated linear modelling of methylation patterns or their correlation with the phenotype and expression patterns. Differentially methylated genes (DMGs) were identified using a contrast against control samples (adjusted p-value <0.001 and |log fold-change of M-value| >2). These results were further filtered using a series of all possible pairwise stage contrasts (p-value <0.05) to obtain stage-specific DMGs. These were then subjected to a consensus analysis, followed by Kaplan-Meier survival analysis to explore the relationship between methylation and prognosis for the consensus stage-salient biomarkers. Results: We found significant genome-wide changes in methylation patterns in cancer samples relative to controls agnostic of stage. Our stage-differentiated analysis yielded the following stage-salient genes: one stage-I gene (FBN1), one stage II specific gene (FOXG1), one stage III specific gene (HCN1) and four stage IV specific genes (NELL1, ZNF135, FAM123A, LAMA1), which could be used for stage-specific diagnosis. All the biomarkers were hypermethylated, indicating down-regulation and signifying a CpG island Methylator Phenotype (CIMP) manifestation. A prognostic signature consisting of FBN1 and FOXG1was significantly associated with patient survival (p-value < 0.01) and could be used as a biomarker panel for early-stage CRC prognosis. Conclusion: Our workflow for stage-differentiated consensus analysis has yielded stage-salient diagnostic biomarkers as well as an early-stage prognostic biomarker panel. In addition, our studies have affirmed a novel CIMP-like signature in colorectal cancer, urging clinical validation.

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RETRACTED ARTICLE: Forkhead box (FOX) G1 promotes hepatocellular carcinoma epithelial-Mesenchymal transition by activating Wnt signal through forming T-cell factor-4/Beta-catenin/FOXG1 complex

Cited by 30 publications

References 36 publications

Cancer stem cell property and gene signature in bone-metastatic Breast Cancer cells

Cancer stem cell property and gene signature in bone-metastatic Breast Cancer cells

For COPD, regulation of miR-515-5p by hsa_circ_0061052, acting via the FoxC1/Snail pathway, is involved in cigarette smoke-induced airway remodeling

Stage-differentiated modelling of methylation patterns uncovers salient biomarkers and prognostic signatures in colorectal cancer progression

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