The impact of DNA demethylation on the upregulation of the NRN1 and TNFAIP3 genes associated with advanced gastric cancer

Wisnieski, Fernanda; Santos, Leonardo Caires; Calcagno, Danielle Queiroz; Geraldis, Jaqueline Cruz; Gigek, Carolina Oliveira; Anauate, Ana Carolina; Chen, Elizabeth; Rasmussen, Lucas Trevizani; Payão, Spencer Luíz Marques; Artigiani, Ricardo; Demachki, Sâmia; Assumpção, Paulo Pimentel de; Lourenço, Laércio Gomes; Arasaki, Carlos Haruo; Pabinger, Stephan; Krainer, Julie; Leal, Mariana Ferreira; Burbano, Rommel Rodrı́guez; Smith, Marı́lia de Arruda Cardoso

doi:10.1007/s00109-020-01902-1

Cited by 15 publications

(6 citation statements)

References 47 publications

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“…The function of TNFAIP3 mainly relies on its ubiquitin degradation for intracellular protein expression (Kim et al 2020). Recent studies suggested that TNFAIP3 may have vital role in the invasion and proliferation of lung cancer and gastric cancer (Liao et al 2020;Wisnieski et al 2020). Our results revealed that the expression of TNFAIP3 was decreased in cancer samples, but decreased more under P, indicating P could reduce in ammation better than S.…”

Section: Discussionmentioning

confidence: 59%

Transcriptome Analysis Reveals the Differential Inflammatory Effects Between Propofol and Sevoflurane During Lung Cancer Resection: a Randomized Pilot Study

Zhang¹,

Wang²,

Cai³

et al. 2021

Preprint

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Background: Propofol and sevoflurane are two commonly used anesthetics perioperatively. It showed that anesthetic drugs may have an effect on tumorigenesis. Previous researches mostly focused on in vitro experiments, the specimens collected were mostly peripheral body fluid, lacking direct evidence of the impact of anesthetic drugs on human tissues. This study aims at elucidating the effects of propofol and sevoflurane on lung cancer using next-generation sequencing through an in vivo experiment. Methods: Patients were randomly assigned to a group either receiving propofol or sevoflurane during surgery. Then patients’ tumor and paired normal samples were collected and sequenced by next-generation sequencing. Differentially expressed genes (DEG) were analyzed by two statistical models, then cluster analysis, PCA, GO ontology and KEGG pathways analysis were done. Candidate genes were confirmed by qRT-PCR. Results: Two study groups demographic data were not statistically significant. Through single factor model analysis, 810 DEG in propofol group and 508 DEG in sevoflurane group were obtained. In order to better reflect the differential effects of propofol and sevoflurane, in the meanwhile reduce false positives of DEG, we used multi-factor model analysis, which resulted in 124 DEG. In PCA and cluster analysis, four groups (propofol cancer group, propofol normal group, sevoflurane cancer group, sevoflurane normal group) were separated adequately, indicating the accuracy of DEG. We chose seven significant pathways (Cellular response to interleukin-1, Chemokine-mediated signaling pathway, Chemokine signaling pathway, Cytokine-cytokine receptor interaction, Inflammatory response, Immune response, TNF signaling pathway) for downstream analysis. From qRT-PCR results, three genes (CXCR1, CXCL8 and TNFAIP3) were confirmed. Conclusions: Through RNA-seq analysis, the effects of propofol and sevoflurane during lung cancer resection were different, and mainly differ in inflammatory related pathways which might be possibly by targeting CXCL8.Trial registration: Trial registry number was ChiCTR1900026213 (http://www.chictr.org.cn/showproj.aspx?proj=43733).

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Section: Discussionmentioning

confidence: 59%

Transcriptome Analysis Reveals the Differential Inflammatory Effects Between Propofol and Sevoflurane During Lung Cancer Resection: a Randomized Pilot Study

Zhang¹,

Wang²,

Cai³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…The function of TNFAIP3 mainly relies on its ubiquitin degradation to regulate intracellular protein expression [ 32 ]. Recent studies suggested that TNFAIP3 may have a vital role in the invasion and proliferation of lung cancer and gastric cancer [ 31 , 33 ]. Our results revealed that the expression of TNFAIP3 was decreased in cancer samples but decreased more under P, indicating that P could reduce inflammation better than S.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis reveals the differential inflammatory effects between propofol and sevoflurane during lung cancer resection: a randomized pilot study

Wang

Cai

et al. 2023

World J Surg Onc

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Background Propofol and sevoflurane are two commonly used perioperative anesthetics. Some studies have found that these anesthetic drugs affect tumorigenesis. Previous studies have mostly focused on in vitro experiments, and the specimens collected were mainly peripheral body fluids, lacking direct evidence of the impact of anesthetic drugs on human tissues. This study aimed to elucidate the effects of propofol and sevoflurane on lung cancer using next-generation sequencing through an in vivo experiment. Methods Patients were randomly assigned to a group receiving either propofol or sevoflurane during surgery. Then, the patients’ tumor and paired normal samples were collected and sequenced by next-generation sequencing. Differentially expressed genes (DEG) were analyzed by two statistical models, followed by cluster analysis, PCA, Gene Ontology, and KEGG pathway analysis. Candidate genes were confirmed by qRT–PCR. Results The demographic data of the two study groups were not statistically significant. Through single-factor model analysis, 810 DEG in the propofol group and 508 DEG in the sevoflurane group were obtained. To better reflect the differential effects between propofol and sevoflurane while reducing the false-positive DEG, we used multifactor model analysis, which resulted in 124 DEG. In PCA and cluster analysis, four groups (propofol cancer group, propofol normal group, sevoflurane cancer group, sevoflurane normal group) were separated adequately, indicating the accuracy of the analysis. We chose seven significant pathways (cellular response to interleukin-1, chemokine-mediated signaling pathway, chemokine signaling pathway, cytokine–cytokine receptor interaction, inflammatory response, immune response, and TNF signaling pathway) for downstream analysis. Based on the pathway analysis, three candidate genes (CXCR1, CXCL8, and TNFAIP3) were chosen, and their qRT–PCR results were consistent with the sequencing results. Conclusions Through RNA-seq analysis, the effects of propofol and sevoflurane during lung cancer resection were different, mainly in inflammatory-related pathways, which might be possibly by targeting CXCL8. Trial registration Trial registry number was ChiCTR1900026213.

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“…DNA hypomethylation and histone hyperacetylation at the A20 promoter can activate A20 expression in Zn-supplemented hens [ 29 ]. Inverse correlations between the A20 mRNA and DNA methylation levels in its intron indicated that increased A20 expression seems to be regulated by DNA demethylation in GC samples [ 30 ]. The downregulation of A20 in CD4 + T cells from systemic lupus erythematosus was closely associated with demethylation of histone H3K4, which led to a decreased amount of H3K4me3 in the promoter of the A20 gene [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Decreased ubiquitin modifying enzyme A20 associated with hyper-responsiveness to ovalbumin challenge following intrauterine growth restriction

Zheng

et al. 2023

Respir Res

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Background Intrauterine growth restriction (IUGR) is strongly correlated with an increased risk of asthma later in life. Farm dust protects mice from developing house dust mite-induced asthma, and loss of ubiquitin modifying enzyme A20 in lung epithelium would abolish this protective effect. However, the mechanisms of A20 in the development of asthma following IUGR remains unknown. Methods An IUGR rat model induced by maternal nutrient restriction was used for investigating the role of A20 in the response characteristics of IUGR rats to ovalbumin (OVA) challenge. The ubiquitination of proteins and N6-methyladenosine (m6A) modifications were used to further assess the potential mechanism of A20. Results IUGR can reduce the expression of A20 protein in lung tissue of newborn rats and continue until 10 weeks after birth. OVA challenging can increase the expression of A20 protein in lung tissue of IUGR rats, but its level was still significantly lower than the control OVA group. The differentially ubiquitinated proteins in lung tissues were also observed in IUGR and normal newborn rats. Furthermore, this ubiquitination phenomenon continued from the newborn to adulthood. In the detected RNA methylations, m6A abundance of the motif GGACA was the highest. The higher abundances of m6A modification of A20 mRNA from IUGR were negatively correlated with the trend of A20 protein levels. Conclusion These findings indicate A20 as a key regulator during the development of asthma following IUGR, providing further insight into the prevention of asthma induced by environmental factors.

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The impact of DNA demethylation on the upregulation of the NRN1 and TNFAIP3 genes associated with advanced gastric cancer

Cited by 15 publications

References 47 publications

Transcriptome Analysis Reveals the Differential Inflammatory Effects Between Propofol and Sevoflurane During Lung Cancer Resection: a Randomized Pilot Study

Transcriptome Analysis Reveals the Differential Inflammatory Effects Between Propofol and Sevoflurane During Lung Cancer Resection: a Randomized Pilot Study

Transcriptome analysis reveals the differential inflammatory effects between propofol and sevoflurane during lung cancer resection: a randomized pilot study

Decreased ubiquitin modifying enzyme A20 associated with hyper-responsiveness to ovalbumin challenge following intrauterine growth restriction

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