Hypoxia-Related Gene FUT11 Promotes Pancreatic Cancer Progression by Maintaining the Stability of PDK1

Cao, Wenpeng; Zeng, Zhirui; Pan, Runsang; Wu, Hao; Zhang, Xiangyan; Chen, Hui; Nie, Yingjie; Zhou, Yu; Lei, Shan

doi:10.3389/fonc.2021.675991

Cited by 16 publications

(14 citation statements)

References 31 publications

(30 reference statements)

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“…These results suggest that MGAT4B is a tumor-promoting factor and is closely associated with a tumor-suppressive immune state. As for other GT genes belonging to our model, B3GNT8 was associated with malignancy and metastasis of glioma [27], while FUT11 [28], FUT4 [29], GALNT16 [30], GALNT8 [31], MGAT4C [32], and PIGV [33] have been individually studied in various type of tumors previously and are correlated with tumor malignancy, proliferation, cancer stem cells, and immune cell attraction.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis Identified Glycosyltransferase Signature to Predict Glioma Prognosis and TAM Phenotype

Liu

et al. 2023

BioMed Research International

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Glycosylation is the most common posttranslational modification of proteins. Glycosyltransferase gene differential expression dictates the glycosylation model and is epigenetically regulating glioma progression and immunity. This study is aimed at identifying the glycosyltransferase gene signature to predict the prognosis and immune characteristics of glioma. The glycosyltransferase gene signature of glioma was identified in the TCGA database and validated in the CGGA database. Glioma patients were then divided into high- and low-risk groups based on risk scores to compare survival differences and predictive capacity. Subsequently, validation of glycosyltransferase gene signature merits by comparing with other signatures and utility in clinical judgment. The immune cell infiltration, immune pathways, and immune checkpoint expression level were also analyzed and compared in the high- and low-risk groups. Finally, the signature and its gene function were tested in our cohort and in vitro experiments. Eight glycosyltransferase genes were identified to establish the glycosyltransferase signature to predict the prognosis of glioma patients. The survival time was shorter in the high-risk group compared to the low-risk group based on glycosyltransferase signature and was confirmed in an independent external cohort. The glycosyltransferase signature displayed outstanding predictive capacity than other signatures in the TCGA and CGGA database cohorts. Furthermore, patients in the high-risk group were positively correlated with TAM infiltration, immune checkpoint expression level, and protumor immune pathways in TCGA cohorts. Validation of clinical tissue specimens revealed that the high-risk group was closely associated with infiltration of M2 TAMs. High-risk genes in the signature promote glioma proliferation, invasion, and macrophage recruitment in an in vitro validation of U87 and U251 cell lines. This carefully constructed that glycosyltransferase signature can predict the prognosis and immune profile of gliomas and help us evaluate subsequent macrophage-targeted therapies as well as other immune microenvironment modulation therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis Identified Glycosyltransferase Signature to Predict Glioma Prognosis and TAM Phenotype

Liu

et al. 2023

BioMed Research International

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“…Mice were feed in specified pathogen free environment with 12 h light and 12 h dark. Protocol subcutaneous tumorigenesis model and pulmonary metastasis model were accordance with previous studies [ 23 , 24 ]. In briefly, to measure proliferation in vivo , HepG2 cells were resuspended in PBS, the density was adjusted to 1 × 10 7 /mL and 200 μL of each cell suspension was injected into the right flanks of mice (n = 8/group).…”

Section: Methodsmentioning

confidence: 99%

A novel hypoxia-driven gene signature that can predict the prognosis of hepatocellular carcinoma

et al. 2022

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Hypoxia environment exists in already started hepatocellular carcinoma (HCC) and promotes its progression by driving changes in the gene expression profiles of cells. However, the status of hypoxia-driven genes in HCC is largely unknown. In the present study, 368 HCC tissues from The Cancer Genome Atlas were divided into high and low hypoxia groups according to their hypoxia signatures. A total of 1,142 differentially expressed genes (DEGs) were identified between the two groups, and 34 of these DEGs were highly expressed in HCC tissues compared with adjacent tissues, especially in HCC tissues from patients with stage III–IV HCC. After constructing a protein–protein interaction network and applying the least absolute shrinkage and selection operator Cox regression method for 34 DEGs, a three-gene signature (complement factor H related 3 [ CFHR3 ], egl-9 family hypoxia inducible factor 3 [ EGLN3 ], and chromogranin A [ CHGA ]) was constructed and had prognostic value to predicted outcome of patients with HCC. This three-gene signature was suitable for classifying patients with HCC in the International Cancer Genome Consortium. CFHR3 shows remarkable diagnostic value in HCC. Hypoxia decreased CFHR3 expression, but increased HCC cell proliferation and motility. Overexpression of CFHR3 in HCC cells under hypoxia reversed the stimulatory effects of hypoxia and suppressed cell proliferation and metastasis in vivo . In conclusion, we identified a novel hypoxia-driven gene signature ( CFHR3, EGLN3 , and CHGA ) for reliable prognostic prediction of HCC, and demonstrated that overexpression of CFHR3 may be a potential strategy to overcome hypoxia and treat HCC.

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“…The downregulation of these genes could be contributing to the decreased reliance of hypoxic cells on the oxidative respiratory chain performed through mitochondrial function. The remaining thirteen genes were consistently upregulated in all the cell lines, and included known HIF-1α activated genes, such as PGK1 ( Li et al, 1996 ) and PDK1 ( Kim et al, 2006 ) that play significant roles in the metabolic switch to glycolysis; FUT11 ( Cao et al, 2021 ; Ruan et al, 2021 )and KCTD11 ( Leithner et al, 2014 ; Cao et al, 2021 ), involved in proliferation; ADM involved in invasion and angiogenesis ( Keleg et al, 2007 ); NDRG1 involved in apoptosis ( Guo et al, 2020 ) and P4HA1 playing a role in ECM remodeling ( Gilkes et al, 2013 ). Of interest, the peptidylglycine alpha-amidating monooxygenase, PAM , has been reported as another oxygen sensing molecule that is activated in mild hypoxia and is involved in the C-terminal amidation of peptides that is necessary for their stability and biological function ( Simpson et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Chronic hypoxia is associated with transcriptomic reprogramming and increased genomic instability in cancer cells

Khouzam

Sharda²,

Rao³

et al. 2023

Front. Cell Dev. Biol.

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Hypoxia afflicts the microenvironment of solid tumors fueling malignancy. We investigated the impact of long hypoxia exposure on transcriptional remodeling, tumor mutational burden (TMB), and genomic instability of cancer cells that were grouped based on their inherent sensitivity or resistance to hypoxia. A hypoxia score was used as a metric to distinguish between the most hypoxia-sensitive (hypoxia high (HH)), and most resistant (hypoxia low (HL)) cancer cells. By applying whole exome sequencing and microarray analysis, we showed that the HH group was indeed more sensitive to hypoxia, having significantly higher TMB (p = 0.03) and copy number losses (p = 0.03), as well as a trend of higher transcriptional response. Globally cells adapted by decreasing expression of genes involved in metabolism, proliferation, and protein maturation, and increasing alternative splicing. They accumulated mutations, especially frameshift insertions, and harbored increased copy number alterations, indicating increased genomic instability. Cells showing highest TMB simultaneously experienced a significant downregulation of DNA replication and repair and chromosomal maintenance pathways. A sixteen-gene common response to chronic hypoxia was put forth, including genes regulating angiogenesis and proliferation. Our findings show that chronic hypoxia enables survival of tumor cells by metabolic reprogramming, modulating proliferation, and increasing genomic instability. They additionally highlight key adaptive pathways that can potentially be targeted to prevent cancer cells residing in chronically hypoxic tumor areas from thriving.

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Hypoxia-Related Gene FUT11 Promotes Pancreatic Cancer Progression by Maintaining the Stability of PDK1

Cited by 16 publications

References 31 publications

Comprehensive Analysis Identified Glycosyltransferase Signature to Predict Glioma Prognosis and TAM Phenotype

Comprehensive Analysis Identified Glycosyltransferase Signature to Predict Glioma Prognosis and TAM Phenotype

A novel hypoxia-driven gene signature that can predict the prognosis of hepatocellular carcinoma

Chronic hypoxia is associated with transcriptomic reprogramming and increased genomic instability in cancer cells

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