Depletion of VAX2 restrains the malignant progression of papillary thyroid carcinoma by modulating ERK signaling pathway

Guo, Bei; Zhang, Yi; Yuan, Kun; Jiang, Feng-xia; Cui, Qianbo; Qi-xin, Zhou; Hua, Dong; Chen, Wei; Yang, Shi Yu

doi:10.1515/biol-2019-0027

Cited by 3 publications

(5 citation statements)

References 28 publications

(16 reference statements)

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“…SIX1 has been shown to be upregulated in thyroid cancers and associated with tumor size and metastasis 70 . Papillary thyroid carcinomas show an upregulation in VAX2 71 , and its development is facilitated by CERS6 72 . HHEX is considered a tumor suppressor gene in the thyroid and plays a crucial role in development of the gland 73 .…”

Section: Discussionmentioning

confidence: 99%

Homeobox and Polycomb target gene methylation in human solid tumors

Blanchett,

Lau,

Pfeifer

2024

Sci Rep

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DNA methylation is an epigenetic mark that plays an important role in defining cancer phenotypes, with global hypomethylation and focal hypermethylation at CpG islands observed in tumors. These methylation marks can also be used to define tumor types and provide an avenue for biomarker identification. The homeobox gene class is one that has potential for this use, as well as other genes that are Polycomb Repressive Complex 2 targets. To begin to unravel this relationship, we performed a pan-cancer DNA methylation analysis using sixteen Illumina HM450k array datasets from TCGA, delving into cancer-specific qualities and commonalities between tumor types with a focus on homeobox genes. Our comparisons of tumor to normal samples suggest that homeobox genes commonly harbor significant hypermethylated differentially methylated regions. We identified two homeobox genes, HOXA3 and HOXD10, that are hypermethylated in all 16 cancer types. Furthermore, we identified several potential homeobox gene biomarkers from our analysis that are uniquely methylated in only one tumor type and that could be used as screening tools in the future. Overall, our study demonstrates unique patterns of DNA methylation in multiple tumor types and expands on the interplay between the homeobox gene class and oncogenesis.

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Section: Discussionmentioning

confidence: 99%

Homeobox and Polycomb target gene methylation in human solid tumors

Blanchett,

Lau,

Pfeifer

2024

Sci Rep

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“…A number of studies have documented the dysregulated expression of transcription factor genes in diverse cancer types, including GC [ 7 , 35 , 36 ]. Previous studies have reported that proteins from transcription factor genes regulate lncRNA transcription during tumor progression [ 14 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Norgett et al reported that VAX2 may be associated with distal renal tubular acidosis [ 38 ]. Furthermore, the depletion of VAX2 significantly inhibits the proliferation, migration, and invasion of PTC cells [ 7 ]. However, the function and mechanism of VAX2 in GC remain unclear.…”

Section: Discussionmentioning

confidence: 99%

“…The ventral anterior homeobox 2 (VAX2) gene is specifically expressed in the ventral region of the prospective neural retina in vertebrates [ 4 – 6 ]. A previous report indicated that VAX2 is elevated in papillary thyroid carcinoma (PTC) samples in comparison to normal thyroid tissues, and reducing VAX2 expression significantly inhibits the malignant biological behaviors of PTC cells [ 7 ]. The VAX2 gene encodes a protein that contains a homeodomain and is classified as a homeobox transcription factor [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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The VAX2-LINC01189-hnRNPF signaling axis regulates cell invasion and migration in gastric cancer

Hong,

Yang,

Zhang

et al. 2023

Cell Death Discov.

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Transcription factors (TFs) and long noncoding RNAs (lncRNAs) contribute to gastric cancer (GC). However, the roles of TFs and lncRNAs in the invasion and metastasis of GC remain largely unknown. Here, we observed that the transcription factor VAX2 is significantly upregulated in GC cells and tissues and acts as an oncogene. Moreover, high VAX2 expression is associated with the advancement of tumors in GC. In terms of functionality, the enforced expression of VAX2 promotes the proliferation and metastasis of GC cells. Mechanistically, VAX2 specifically interacts with the LINC01189 promoter and represses LINC01189 transcription. Furthermore, LINC01189 exhibits significant downregulation in GC and functions as a suppressor gene. Functionally, it inhibits migratory and invasive abilities in GC cells. In the context of GC metastasis, VAX2 plays a role in modulating it by trans-repressing the expression of LINC01189. Additionally, LINC01189 binds to hnRNPF to enhance hnRNPF degradation through ubiquitination. The cooperation between LINC01189 and hnRNPF regulates GC cell invasion and migration. In addition, both VAX2 and hnRNPF are highly expressed, while LINC01189 is expressed in at low levels in GC tissues compared to normal gastric tissues. Our study suggests that VAX2 expression facilitates, while LINC01189 expression suppresses, metastasis and that the VAX2-LINC01189-hnRNPF axis plays a contributory role in GC development.

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“…Ventral Anterior Homeobox 2 (VAX2) is a transcription factor that regulates the dorsoventral specifica-tion of the forebrain and Wnt signaling [32,33]. The VAX2 has recently attracted many attentions in cancers and has been proved to regulate the malignant progression of thyroid cancer [34], breast cancer [35], and bladder cancer [36]. Src Homology 2 Domain Containing Transforming Protein (SHD) was over expressed in the cortex and frontal cortex, having a close relationship with spinal muscular atrophy type IV.…”

Section: Discussionmentioning

confidence: 99%

Protective Prognostic Biomarkers Negatively Correlated with Macrophage M2 Infiltration in Low-Grade Glioma

Zhu

Song

Wang

et al. 2022

Journal of Oncology

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Tumor-associated Macrophages (TAMs) play a vital role in the progression of glioma. Macrophage M2 has been confirmed to promote immunosuppression and proliferation of low-grade glioma (LGG). Here, we searched for genes negatively correlated with Macrophages M2 by bioinformatical methods and investigated their protective ability for prognosis. LGG and adjacent normal samples were screened out in TCGA and three GEO datasets. 326 overlapped differentially expressed genes were calculated, and their biological functions were investigated by Go and KEGG analyses. Macrophage M2 accounted for the highest proportion among all 22 immune cells by CIBERSORT deconvolution algorithm. The proportion of Macrophage M2 in LGG was also higher than that in normal tissue according to several deconvolution algorithms. 43 genes in the blue module negatively correlated with Macrophage M2 infiltration were identified by weighted gene coexpression network analysis (WGCNA). Through immune infiltration and correlation analysis, FGFBP3, VAX2, and SHD were selected and they were enriched in G protein-coupled receptors’ signaling regulation and cytokine receptor interaction. They could prolong the overall and disease-free survival time. Univariate and multivariate Cox regression analyses were applied to evaluate prognosis prediction ability. Interestingly, FGFBP3 and AHD were independent prognostic predictors. A nomogram was drawn, and its 1-year, 3-year, and 5-year survival prognostic value was verified by ROC curves and calibration plots. In conclusion, FGFBP3, VAX2, and SHD were protective prognostic biomarkers against Macrophage M2 infiltration in low-grade glioma. The FGFBP3 and SHD were independent factors to effectively predict long-term survival probability.

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Depletion of VAX2 restrains the malignant progression of papillary thyroid carcinoma by modulating ERK signaling pathway

Cited by 3 publications

References 28 publications

Homeobox and Polycomb target gene methylation in human solid tumors

Homeobox and Polycomb target gene methylation in human solid tumors

The VAX2-LINC01189-hnRNPF signaling axis regulates cell invasion and migration in gastric cancer

Protective Prognostic Biomarkers Negatively Correlated with Macrophage M2 Infiltration in Low-Grade Glioma

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