Global DNA methylation screening of liver in piperonyl butoxide-treated mice in a two-stage hepatocarcinogenesis model

Yafune, Atsunori; Kawai, Masaomi; Itahashi, Megu; Kimura, Masayuki; Nakane, Fumiyuki; Mitsumori, Kunitoshi; Shibutani, Makoto

doi:10.1016/j.toxlet.2013.08.006

Cited by 23 publications

(22 citation statements)

References 28 publications

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“…In the current study, both enantiomers of fipronil induced obvious changes in global DNA methylation. However, the S-(+)-enantiomer altered global DNA methylation more than the R-(−)-enantiomer, and pesticides with greater toxicity had more pronounced effects on DNA methylation 48, 49 .…”

Section: Discussionmentioning

confidence: 97%

“…Similarly, TGF β and its superfamily members, the Nodal proteins, play important roles in mesendoderm induction and dorsoventral/anteroposterior patterning through their interaction with smad2 and smad3 during early vertebrate embryo development 55 . Additionally, the vascular smooth muscle contraction pathway is highly associated with the development of swimbladders in zebrafish larvae (swimbladders are highly vascularized organs) 48 . The cross talk between Hedgehog and Wnt signaling is necessary for the formation and organization of all three tissues layers of the swimbladder 49 .…”

Section: Discussionmentioning

confidence: 99%

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Fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation

Qian

Wang

et al. 2017

Sci Rep

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Enantioselectivity in the aquatic toxicity of chiral pesticides has been widely investigated, while the molecular mechanisms remain unclear. Thus far, few studies has focused on genomic expression related to selective toxicity in chiral pesticide, nor on epigenetic changes, such as DNA methylation. Here, we used fipronil, a broad-spectrum insecticide, as a model chemical to probe its enantioselective toxicity in embryo development. Our results showed that S-(+)-fipronil caused severer developmental toxicity in embryos. The MeDIP-Seq analysis demonstrated that S-(+)-fipronil dysregulated a higher level of genomic DNA methylation than R-(−)-fipronil. Gene Ontology analysis revealed that S-(+)-fipronil caused more differentially methylated genes that are involved in developmental processes. Compared with R-(−)-fipronil, S-(+)-fipronil significantly disrupted 7 signaling pathways (i.e., mitogen-activated protein kinases, tight junctions, focal adhesion, transforming growth factor-β, vascular smooth muscle contraction, and the hedgehog and Wnt signaling pathways) by hyper-methylation of developmentally related genes, which further induced the downregulation of those genes. Together, these data suggest that differences in DNA methylation may partly explain the enantioselectivity of fipronil to zebrafish embryos. The application of epigenetics to investigate the enantioselective toxicity mechanism of chiral chemicals would provide a further understanding of their stereoselectivity biological effects.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation

Qian

Wang

et al. 2017

Sci Rep

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“…16 CMTM3 and CMTM5 are associated with tumorigenesis. 17,18 CMTM6 is involved in the DNA methylation of hepatocellular carcinoma 19 and CMTM6 overexpression is associated with prognosis in glioma 20 and hepatocellular carcinoma. 21 Recently, two studies reported that CMTM6 regulated antitumor immunity by maintaining the expression of PD-L1.…”

Section: Discussionmentioning

confidence: 99%

Increased CMTM6 can predict the clinical response to PD-1 inhibitors in non-small cell lung cancer patients

et al. 2019

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CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) plays a crucial role in the stability of the programmed death-ligand 1 (PD-L1). However, there has been no previous study of CMTM6 in non-small cell lung cancer (NSCLC) and its association with PD-L1 has not been confirmed. The aim of this study was to investigate the expression of CMTM6 and PD-L1 and to confirm their predictive roles for anti-PD-1 therapy in non-small cell lung cancer. CMTM6 and PD-L1 immunohistochemical expressions were evaluated in 35 advanced, treatment-refractory NSCLC patients who received PD-1 inhibitor therapy. The correlation between CMTM6 and PD-L1 expression was also determined based on immunohistochemistry and RNA-sequencing data obtained from The Cancer Genome Atlas (TCGA) database. CMTM6 expression was positively correlated with PD-L1 expression in immunohistochemical data (Pearson's r = 0.342 and p = .044). A positive correlation was also identified in the mRNA expression data. Using receiver operating characteristic curves, the levels of CMTM6 and PD-L1 expression which provided the best distinguishing point between responder versus non-responder to PD-1 inhibitors were 70 and 75 H-scores, respectively. The patients in the PD-1 inhibitor responder group had higher CMTM6 expressions in univariate logistic regression analysis (odds ratio (OR) = 5.333, p = .037). However, PD-L1 expression was not associated with response to PD-1 inhibitor (p = .288). In multivariate analysis, CMTM6 was also found to be an independent predictor of the response to PD-1 inhibitors (OR = 6.226, p = .032). CMTM6 expression can be a promising predictor useful for therapeutic decision-making regarding PD-1 inhibitors.

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Section: Discussionmentioning

confidence: 99%

“…We have recently found hypermethylation of Wdr6, which also belongs to this protein family, in the promoter region in non-neoplastic hepatocytes of mice promoted with piperonyl butoxide, a non-genotoxic hepatocarcinogen, for 25 weeks in a two-stage hepatocarcinogenesis model (Yafune et al, 2013a). Wdr6 has been implicated in cell growth arrest through interaction with serine/threonine kinase 11 (Xie et al, 2007), and we have also found increased expression in both preneoplastic and neoplastic liver lesions in contrast to the lack of Wdr6 expression in non-neoplastic liver cells in mice (Yafune et al, 2013a). We have also reported that the proportion of GST-P + foci increased in preneoplastic cellular populations with cell cycle disruption at both G 1 /S and G 2 /M, which permitted clonal selection of proliferative foci resulting in the acquisition of multiple aberrant phenotypes consistent with disrupted checkpoint function by TAA promotion (Tsuchiya et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Promoter-region hypermethylation and expression downregulation of Yy1 (Yin yang 1) in preneoplastic liver lesions in a thioacetamide rat hepatocarcinogenesis model

Abe¹,

Ogawa²,

Wang³

et al. 2014

Toxicology and Applied Pharmacology

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Global DNA methylation screening of liver in piperonyl butoxide-treated mice in a two-stage hepatocarcinogenesis model

Cited by 23 publications

References 28 publications

Fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation

Fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation

Increased CMTM6 can predict the clinical response to PD-1 inhibitors in non-small cell lung cancer patients

Promoter-region hypermethylation and expression downregulation of Yy1 (Yin yang 1) in preneoplastic liver lesions in a thioacetamide rat hepatocarcinogenesis model

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