Proteomic characteristics and identification of PM2.5-induced differentially expressed proteins in hepatocytes and c-Myc silenced hepatocytes

Qin, Shuangjian; Li, Boru; Li, Runbing; Cai, Ying; Zheng, Kai; Huang, Haiyan; Xiao, Fang; Zeng, Ming; Xu, Xinyun

doi:10.1016/j.ecoenv.2020.111838

Cited by 6 publications

(6 citation statements)

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“…Thus, in p53 +/+ Eμ-Myc male pre-tumoral splenocytes, an increased Ackr4 expression might delay lymphomagenesis in part by attenuating Myc signalling. Indeed, the observed lower expression of Mt2, known to be regulated by Myc (Qin et al, 2021 ), appears consistent with this hypothesis. Importantly, Ackr4 was previously found to inhibit the growth and metastasis of breast, cervical, colorectal, hepatocellular and nasopharyngeal cancer cells (Feng et al, 2009 ;Hou et al, 2013 ;Ju et al, 2019 ;Shi et al, 2015 ;Zhu et al, 2014 ), although no report mentioned any sex-specific bias for cancers occurring in both sexes.…”

Section: Discussionsupporting

confidence: 83%

“…However, ChIP-Atlas reported no binding of these proteins at the Mt2 promoter. Alternatively, evidence that Myc may impact on Mt2 expression was obtained previously (Qin et al, 2021 ), and ChIP-Atlas reported Myc binding at the Mt2 promoter in primary B-cells from lymph nodes of Eμ-Myc mice as well as Eμ-Mycinduced lymphoma cells (Figure S3D). This may suggest that the lower expression of Mt2 in pretumoral splenic cells from p53 +/+ Eμ-Myc males (Figure 3E ) might result from a subtle difference in Myc signalling.…”

Section: Transcriptomes From P53 +/+ Eμ-myc and P53 δAs/δas Eμ-myc Ma...mentioning

confidence: 56%

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Mutant mice lacking alternatively spliced p53 isoforms unveil Ackr4 as a male-specific prognostic factor in Myc-driven B-cell lymphomas

Fajac,

Simeonova,

Leemput

et al. 2024

eLife

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The gene encoding p53, a major tumor suppressor protein, encodes several alternative isoforms of elusive biological significance. Here we show that mice lacking the Trp53 Alternatively Spliced (AS) exon, thereby expressing the canonical p53 protein but not isoforms with the AS C-terminus, have unexpectedly lost a male-specific protection against Myc-induced B-cell lymphomas. Lymphomagenesis was delayed in p53 +/+ Eμ-Myc males compared to p53 ΔAS/ΔAS Eμ-Myc males, but also compared to p53 +/+ Eμ-Myc and p53 ΔAS/ΔAS Eμ-Myc females. Pre-tumoral splenocytes from p53 +/+ Eμ-Myc males exhibited a higher expression of Ackr4, encoding an atypical chemokine receptor with tumor suppressive effects. We show that Ackr4 is a p53 target gene, but that its p53-mediated transactivation is inhibited by estrogens. We identify Ackr4 as a male-specific factor of good prognosis, relevant for murine Eμ-Myc-induced and human Burkitt lymphomas. These data demonstrate the functional relevance of alternatively spliced p53 isoforms and reveal sex disparities in Myc-driven B-cell lymphomagenesis.

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Section: Discussionsupporting

confidence: 83%

Section: Transcriptomes From P53 +/+ Eμ-myc and P53 δAs/δas Eμ-myc Ma...mentioning

confidence: 56%

Mutant mice lacking alternatively spliced p53 isoforms unveil Ackr4 as a male-specific prognostic factor in Myc-driven B-cell lymphomas

Fajac,

Simeonova,

Leemput

et al. 2024

eLife

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show abstract

“…Thus, in p53 +/+ Eμ-Myc male pre-tumoral splenocytes, an increased Ackr4 expression might delay lymphomagenesis in part by attenuating Myc signalling. Indeed, the observed lower expression of Mt2, known to be regulated by Myc (Qin et al, 2021), appears consistent with this hypothesis. Importantly, Ackr4 was previously found to inhibit the growth and metastasis of breast, cervical, colorectal, hepatocellular and nasopharyngeal cancer cells (Feng et al, 2009;Hou et al, 2013;Ju et al, 2019;Shi et al, 2015;Zhu et al, 2014), although no report mentioned any sex-specific bias for cancers occurring in both sexes.…”

Section: Discussionsupporting

confidence: 83%

“…As mentioned before, the ACKR4-mediated sequestration of CCL21 may impair the CCR7 signalling cascade, which might lead to decreased MYC activity (Shi et al, 2015). In p53 +/+ Eμ-Myc male splenic cells, the observed lower expression of Mt2, known to be regulated by Myc (Qin et al, 2021), and of many genes that are hallmark Myc targets (as revealed by GSEA), appear consistent with this hypothesis. In addition, Ccr7 is required for lymphoma cell lodging to secondary lymphoid organs (Rehm et al, 2011) and ACKR4 expression was inversely correlated with the metastasis capacity of different types of cancer cells (Shi et al, 2015;Zhu et al, 2014).…”

Section: Discussionsupporting

confidence: 81%

Mutant mice lacking alternatively spliced p53 isoforms unveilAckr4as a male-specific prognostic factor in Myc-driven B-cell lymphomas

Fajac,

Simeonova,

Leemput

et al. 2023

Preprint

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The gene encoding p53, a major tumor suppressor protein, encodes several alternative isoforms of elusive biological significance. Here we show that mice lacking the Trp53 Alternatively Spliced (AS) exon, thereby expressing the canonical p53 protein but not isoforms with the AS C-terminus, have unexpectedly lost a male-specific protection against Myc-induced B-cell lymphomas. Lymphomagenesis was delayed in p53+/+ Eu-Myc males compared to p53DeltaAS/DeltaAS Eu-Myc males, but also compared to p53+/+ Eu-Myc and p53DeltaAS/DeltaAS Eu-Myc females. Pre-tumoral splenocytes from p53+/+ Eu-Myc males exhibited a higher expression of Ackr4 encoding an atypical chemokine receptor with tumor suppressive effects. We show that Ackr4 is a p53 target gene, but that its p53-mediated transactivation is inhibited by estrogens. We identify Ackr4 as a male-specific factor of good prognosis, relevant for murine Eu-Myc-induced and human Burkitt lymphomas. These data demonstrate the functional relevance of alternatively spliced p53 isoforms and reveal sex disparities in Myc-driven B-cell lymphomagenesis.

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“…Previously, current smokers have shown hypermethylation of cg23771366 [17], located in the serine protease 23 (PRSS23) gene, which encodes a conserved member of the trypsin family of serine proteases [18]. Abnormal regulation of serine protease activity could lead to pathological conditions such as cancer [19]; in vitro assays have also proposed PRSS23 as a potential biomarker of exposure to PM2.5 and reaffirmed its contribution to cancer development [18].…”

Section: Introductionmentioning

confidence: 99%

Hypomethylation of AHRR (cg05575921) Is Related to Smoking Status in the Mexican Mestizo Population

Bravo-Gutiérrez

Falfán-Valencia

Ramírez‐Venegas

et al. 2021

Genes

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Tobacco smoking results in a multifactorial disease involving environmental and genetic factors; epigenome-wide association studies (EWAS) show changes in DNA methylation levels due to cigarette consumption, partially reversible upon tobacco smoking cessation. Therefore, methylation levels could predict smoking status. This study aimed to evaluate the DNA methylation level of cg05575921 (AHRR) and cg23771366 (PRSS23) and their correlation with lung function variables, cigarette consumption, and nicotine addiction in the Mexican smoking population. We included 114 non-smokers (NS) and 102 current tobacco smokers (TS); we then further subclassified them as heavy smokers (HS) (n = 53) and light smokers (LS) (n = 49). We used restriction enzymes (MspI/HpaII) and qPCR to determine the DNA methylation level. We observed significant hypomethylation of cg05575921 in smokers compared to NS (p = 0.003); further analysis found a difference between HS and NS (p = 0.02). We did not observe differences between other groups or a positive correlation between methylation levels and age, BMI, cigarette consumption, nicotine addiction, or lung function. In conclusion, the cg05575921 site of AHRR is significantly hypomethylated in Mexican smokers, especially in HS (≥20 cigarettes per day).

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Proteomic characteristics and identification of PM2.5-induced differentially expressed proteins in hepatocytes and c-Myc silenced hepatocytes

Cited by 6 publications

References 40 publications

Mutant mice lacking alternatively spliced p53 isoforms unveil Ackr4 as a male-specific prognostic factor in Myc-driven B-cell lymphomas

Mutant mice lacking alternatively spliced p53 isoforms unveil Ackr4 as a male-specific prognostic factor in Myc-driven B-cell lymphomas

Mutant mice lacking alternatively spliced p53 isoforms unveilAckr4as a male-specific prognostic factor in Myc-driven B-cell lymphomas

Hypomethylation of AHRR (cg05575921) Is Related to Smoking Status in the Mexican Mestizo Population

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