Cytochrome P450 2U1 Is a Novel Independent Prognostic Biomarker in Breast Cancer Patients

Luo, Bin; Chen, Chuang; Wu, Xiaoyan; Yan, Dandan; Chen, Fangfang; Yu, Xinxin

doi:10.3389/fonc.2020.01379

Cited by 7 publications

(3 citation statements)

References 33 publications

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“…This was also consistent with the findings of Luo et al. ( 48 ) that higher cytochrome P450 2U1 (CYP2U1) levels were predictive of a poor 5-year OS and were associated with the histopathological grade of BCa. These results suggest that dysregulation of circRNAs in GC may be involved in tumorigenesis.…”

Section: Discussionsupporting

confidence: 92%

Expression and clinical value of circRNAs in serum extracellular vesicles for gastric cancer

Liu

Ding

et al. 2022

Front. Oncol.

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ObjectiveAt present, there are still no effective diagnosis methods for gastric cancer (GC). Increasing evidences indicate that Extracellular Vesicle circular RNAs (EV circRNAs) play a crucial role in several diseases. However, their correlations with GC are not clarified. This study aims to investigate the expression profile of serum EV circRNAs in GC and evaluate its potential clinical value.MethodsHigh-throughput RNA sequencing (RNA-seq) was used to assess circRNA expression profiles between 4 patients with GC and 4 healthy controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to determine the biological functions of differentially expressed (DE) circRNAs. A circRNA-miRNA-mRNA network was constructed using bioinformatics tools. Reverse transcription-quantitative polymerase chain reaction (RT-q)PCR was used to validate the dysregulated circRNAs. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of circRNAs for GC.ResultsA total of 4692 circRNAs were detected in the serum EVs of healthy controls and patients with GC, most of which were novel (98%) and intergenic (52%). 7 circRNAs were upregulated and 4 circRNAs were downregulated (|log2Fold Change| > 2, P < 0.05). GO and KEGG pathway enrichment analyses revealed that DE circRNAs were primarily involved in glutathione metabolism, protein folding, and drug metabolism-cytochrome P450. Of these, 3 circRNAs (Chr10q11, Chr1p11, and Chr7q11) were identified to be significantly overexpressed in patients with GC compared with healthy controls using RT-qPCR. The combination of 3 EV circRNAs and carcinoembryonic antigen (CEA) produced an area under the curve (AUC) of 0.866 (95%CI: 0.803-0.915) with a sensitivity and specificity of 80.4% and 81.8%, respectively. Additionally, the expression levels of 3 EV circRNAs were significantly correlated with tumor size, lymph node metastasis, and TNM stage. The circRNA-miRNA-mRNA network showed that the 3 identified circRNAs were predicted to interact with 13 miRNAs and 91 mRNAs.ConclusionOur results illustrate that the panel of EV circRNAs in serum are aberrantly expressed and may act as the suitable biomarkers for gastric cancer.

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Section: Discussionsupporting

confidence: 92%

Expression and clinical value of circRNAs in serum extracellular vesicles for gastric cancer

Liu

Ding

et al. 2022

Front. Oncol.

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“…CYP2U1 showed hydroxylase activity for fatty acids and N -arachidonoylserine (AS) ( Figure 1D ) ( Dhers et al, 2017 ). Although CYP2U1 has been shown to be involved in some diseases such as breast cancer and hereditary spastic paraplegia, the biological role is still largely unknown ( Luo et al, 2020 ). The cell-specific distribution of CYP ω-hydrolases is key to the local pro-inflammatory effects observed across various diseases.…”

Section: Classification Tissue Distribution and Biological Characteristics Of Cytochrome P450 Omega Hydroxylasesmentioning

confidence: 99%

The Functions of Cytochrome P450 ω-hydroxylases and the Associated Eicosanoids in Inflammation-Related Diseases

Liu

2021

Front. Pharmacol.

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The cytochrome P450 (CYP) ω-hydroxylases are a subfamily of CYP enzymes. While CYPs are the main metabolic enzymes that mediate the oxidation reactions of many endogenous and exogenous compounds in the human body, CYP ω-hydroxylases mediate the metabolism of multiple fatty acids and their metabolites via the addition of a hydroxyl group to the ω- or (ω-1)-C atom of the substrates. The substrates of CYP ω-hydroxylases include but not limited to arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid, epoxyeicosatrienoic acids, leukotrienes, and prostaglandins. The CYP ω-hydroxylases-mediated metabolites, such as 20-hyroxyleicosatrienoic acid (20-HETE), 19-HETE, 20-hydroxyl leukotriene B4 (20-OH-LTB4), and many ω-hydroxylated prostaglandins, have pleiotropic effects in inflammation and many inflammation-associated diseases. Here we reviewed the classification, tissue distribution of CYP ω-hydroxylases and the role of their hydroxylated metabolites in inflammation-associated diseases. We described up-regulation of CYP ω-hydroxylases may be a pathogenic mechanism of many inflammation-associated diseases and thus CYP ω-hydroxylases may be a therapeutic target for these diseases. CYP ω-hydroxylases-mediated eicosanods play important roles in inflammation as pro-inflammatory or anti-inflammatory mediators, participating in the process stimulated by cytokines and/or the process stimulating the production of multiple cytokines. However, most previous studies focused on 20-HETE,and further studies are needed for the function and mechanisms of other CYP ω-hydroxylases-mediated eicosanoids. We believe that our studies of CYP ω-hydroxylases and their associated eicosanoids will advance the translational and clinal use of CYP ω-hydroxylases inhibitors and activators in many diseases.

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“…The function of CYP genes is critical for many metabolic processes, particularly for sex steroid conversion [ 18 ]. The altered expression of CYP genes involved in steroid metabolism may affect sex hormone levels and further increase the risk of some sex-related diseases, such as breast cancer [ 19 ], prostate cancer [ 20 ], infertility [ 21 ], polycystic ovary syndrome [ 22 ], and congenital adrenal hyperplasia [ 23 ]. During pregnancy, fetal sex hormones affect embryo development in many ways.…”

Section: Introductionmentioning

confidence: 99%

Associations Between Cytochrome P450 (CYP) Gene Single-Nucleotide Polymorphisms and Second-to-Fourth Digit Ratio in Chinese University Students

et al. 2021

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Background Cytochrome P450 (CYP) genes are necessary for the production or metabolism of fetal sex hormones during pregnancy. The second-to-fourth digit ratio (2D: 4D) is formed in the early stage of human fetal development and considered an indicator reflecting prenatal sex steroids levels. We explored the association between 2D: 4D and single-nucleotide polymorphisms (SNPs) of CYP. Material/Methods Correlation analysis between 2D: 4D and 8 SNPs, rs2687133 ( CPY3A7 ), rs7173655 ( CYP11A1 ), rs1004467, rs17115149, and rs2486758 ( CYP17A1 ), and rs4646, rs2255192, rs4275794 ( CYP19A1 ), was performed using data from 426 female and 412 male Chinese university students. SNP genotyping was conducted using PCR. Digit lengths were photographed and measured by image processing software. Results rs2486758 ( CYP17A1 ) correlated with left hand 2D: 4D in men ( P =0.026), and rs1004467 ( CYP17A1 ) correlated with right hand 2D: 4D in men ( P =0.008) and the whole population ( P =0.032). In men, allele G rs1004467 decreased right hand 2D: 4D, while allele C of rs2486758 increased left hand 2D: 4D. In women, left hand 2D: 4D was higher in genotypes with allele A of SNP rs4646 ( CYP19A1 ) under the dominant genetic model; female D R-L was higher in genotypes with allele T of rs17115149 ( CYP11A1 ). SNPs rs2687133 ( CYP3A7 ) and rs1004467 ( CYP17A1 ) were significantly correlated with right hand 2D: 4D ( P =0.0107). Conclusions SNPs rs1004467 and rs2486758 of CYP17A1 are significant in the relationship between 2D: 4D and CYP gene polymorphisms under different conditions. SNP interactions between CYP genes probably impact 2D: 4D. The correlation between 2D: 4D and some sex hormone-related diseases may be due to the effect of CYP variants on the 2 phenotypes.

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Cytochrome P450 2U1 Is a Novel Independent Prognostic Biomarker in Breast Cancer Patients

Cited by 7 publications

References 33 publications

Expression and clinical value of circRNAs in serum extracellular vesicles for gastric cancer

Expression and clinical value of circRNAs in serum extracellular vesicles for gastric cancer

The Functions of Cytochrome P450 ω-hydroxylases and the Associated Eicosanoids in Inflammation-Related Diseases

Associations Between Cytochrome P450 (CYP) Gene Single-Nucleotide Polymorphisms and Second-to-Fourth Digit Ratio in Chinese University Students

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