Correlation between global genome methylation and mutation at <scp>CpG</scp> codons of <i>p53</i> gene

Sadeghi, Rouhallah Najjar; Vahedi, Mohsen; Zojaji, Homayoun; Zali, Mohammad Reza

doi:10.1111/1751-2980.12053

Cited by 3 publications

(2 citation statements)

References 32 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, PM2.5 exposure decreased DNMT1 protein level, suggesting that PM2.5-induced down-regulation of DNMT1 may contribute to the reduction of global DNA methylation, although the signaling pathways involved remain to be explored. Hypomethylated DNA sequences in mammal cells are prone to transcriptional activation in response to environmental factors [ 36 , 37 ], and long-term demethylation of many cytosine sites may result in genomic instability, gene mutation or aberrant expression of oncogenes [ 11 , 38 , 39 ]. Hence, we deem that genome-wide DNA hypomethylation may play a crucial role in lung carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Repeated PM2.5 exposure inhibits BEAS-2B cell P53 expression through ROS-Akt-DNMT3B pathway-mediated promoter hypermethylation

Zhou

Tian

et al. 2016

Oncotarget

View full text Add to dashboard Cite

Long-term exposure to fine particulate matter (PM2.5) has been reported to be closely associated with the increased lung cancer risk in populations, but the mechanisms underlying PM-associated carcinogenesis are not yet clear. Previous studies have indicated that aberrant epigenetic alterations, such as genome-wide DNA hypomethylation and gene-specific DNA hypermethylation contribute to lung carcinogenesis. And silence or mutation of P53 tumor suppressor gene is the most prevalent oncogenic driver in lung cancer development. To explore the effects of PM2.5 on global and P53 promoter methylation changes and the mechanisms involved, we exposed human bronchial epithelial cells (BEAS-2B) to low concentrations of PM2.5 for 10 days. Our results indicated that PM2.5-induced global DNA hypomethylation was accompanied by reduced DNMT1 expression. PM2.5 also induced hypermethylation of P53 promoter and inhibited its expression by increasing DNMT3B protein level. Furthermore, ROS-induced activation of Akt was involved in PM2.5-induced increase in DNMT3B. In conclusion, our results strongly suggest that repeated exposure to PM2.5 induces epigenetic silencing of P53 through ROS-Akt-DNMT3B pathway-mediated promoter hypermethylation, which not only provides a possible explanation for PM-induced lung cancer, but also may help to identify specific interventions to prevent PM-induced lung carcinogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Repeated PM2.5 exposure inhibits BEAS-2B cell P53 expression through ROS-Akt-DNMT3B pathway-mediated promoter hypermethylation

Zhou

Tian

et al. 2016

Oncotarget

View full text Add to dashboard Cite

show abstract

“…Thus, the TP53 mutation has been shown to correlate with TP53 hypomethylation status of exons 5–8 [88,89]. Interestingly, methylation of TP53 exons 5–8 can be increased in rat liver and colon mucosa by dietary selenomethionine, with may then influence the preservation of intact TP53 sequence [90].…”

Section: Deregulation Of P53 Through Epigenetic Modificationsmentioning

confidence: 99%

Molecular Mechanisms of p53 Deregulation in Cancer: An Overview in Multiple Myeloma

Herrero

Rojas

Misiewicz-Krzemińska

et al. 2016

IJMS

View full text Add to dashboard Cite

The p53 pathway is inactivated in the majority of human cancers. Although this perturbation frequently occurs through the mutation or deletion of p53 itself, there are other mechanisms that can attenuate the pathway and contribute to tumorigenesis. For example, overexpression of important p53 negative regulators, such as murine double minute 2 (MDM2) or murine double minute 4 (MDM4), epigenetic deregulation, or even alterations in TP53 mRNA splicing. In this work, we will review the different mechanisms of p53 pathway inhibition in cancer with special focus on multiple myeloma (MM), the second most common hematological malignancy, with low incidence of p53 mutations/deletions but growing evidence of indirect p53 pathway deregulation. Translational implications for MM and cancer prognosis and treatment are also reviewed.

show abstract

Promoter hypermethylation of RAR-β tumor suppressor gene in gastric carcinoma: Association with histological type and clinical outcomes

Mohsenzadeh

Sadeghi

Vahedi

et al. 2017

CBM

View full text Add to dashboard Cite

show abstract

Correlation between global genome methylation and mutation at CpG codons of p53 gene

Abstract: As CG → AT transversion at codon 245 is associated with global genome methylation, GG hypomethylation may induce different pattern of mutations, for example, C → A instead of C → T at the CpG codons of the p53 gene during gastritis development in Iranian patients.

Cited by 3 publications

References 32 publications

Repeated PM2.5 exposure inhibits BEAS-2B cell P53 expression through ROS-Akt-DNMT3B pathway-mediated promoter hypermethylation

Repeated PM2.5 exposure inhibits BEAS-2B cell P53 expression through ROS-Akt-DNMT3B pathway-mediated promoter hypermethylation

Molecular Mechanisms of p53 Deregulation in Cancer: An Overview in Multiple Myeloma

Promoter hypermethylation of RAR-β tumor suppressor gene in gastric carcinoma: Association with histological type and clinical outcomes

Contact Info

Product

Resources

About