High frequency of p16 and p14 promoter hypermethylation and marked telomere instability in salivary gland tumors

Nikolic, Nadja; Aničić, Boban; Čarkić, Jelena; Simonović, Jelena; Toljic, Bosko; Tanić, Nasta; Tepavčević, Zvezdana; Vukadinovic, Miroslav; Konstantinović, Vitomir S.; Milašin, Jelena

doi:10.1016/j.archoralbio.2015.08.011

Cited by 18 publications

(17 citation statements)

References 43 publications

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“…The p16 INK4A protein is relatively stable, and its expression is primarily regulated at the transcriptional level. Aberrant hypermethylation of the p16 INK4A gene is widely detected in most tumor types, leading to reduced gene expression 31–33 . In mammalian cells, DNMT1, DNMT3A, and DNMT3B participate in the maintenance of global DNA methylation and gene-specific de novo DNA methylation 34 .…”

Section: Discussionmentioning

confidence: 99%

Particulate matter-induced senescence of skin keratinocytes involves oxidative stress-dependent epigenetic modifications

Ryu¹,

Kang²,

Piao³

et al. 2019

Exp Mol Med

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Ambient air particulate matter (PM) induces senescence in human skin cells. However, the underlying mechanisms remain largely unknown. We investigated how epigenetic regulatory mechanisms participate in cellular senescence induced by PM with a diameter <2.5 (PM2.5) in human keratinocytes and mouse skin tissues. PM2.5-treated cells exhibited characteristics of cellular senescence. PM2.5 induced a decrease in DNA methyltransferase (DNMT) expression and an increase in DNA demethylase (ten–eleven translocation; TET) expression, leading to hypomethylation of the p16INK4A promoter region. In addition, PM2.5 led to a decrease in polycomb EZH2 histone methyltransferase expression, whereas the expression of the epigenetic transcriptional activator MLL1 increased. Furthermore, binding of DNMT1, DNMT3B, and EZH2 to the promoter region of p16INK4A decreased in PM2.5-treated keratinocytes, whereas TET1 and MLL1 binding increased, leading to decreased histone H3 lysine 27 trimethylation (H3K27Me3) and increased H3K4Me3 in the promoter of p16INK4A. PM2.5-induced senescence involved aryl hydrocarbon receptor (AhR)-induced reactive oxygen species (ROS) production. ROS scavenging dampened PM2.5-induced cellular senescence through regulation of DNA and histone methylation. Altogether, our work shows that skin senescence induced by environmental PM2.5 occurs through ROS-dependent the epigenetic modification of senescence-associated gene expression. Our findings provide information for the design of preventive and therapeutic strategies against skin senescence, particularly in light of the increasing problem of PM2.5 exposure due to air pollution.

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Section: Discussionmentioning

confidence: 99%

Particulate matter-induced senescence of skin keratinocytes involves oxidative stress-dependent epigenetic modifications

Ryu¹,

Kang²,

Piao³

et al. 2019

Exp Mol Med

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“…The latest molecular studies have broadened the knowledge on the importance of epigenetic changes associated with salivary gland cancer (SGC) development, in particular DNA methylation, as a mechanism of gene silencing. Kishi et al 13 found, for instance, that RB1 was hypermethylated in 42% of cases of SGC, and Nikolic et al 14 reported that approximately 70% of pleomorphic adenomas harbored hypermethylated p14 and p16. Using a microarray approach, Bell et al 15 also found several highly methylated genes in adenoid cystic carcinoma.…”

mentioning

confidence: 99%

P14 methylation: an epigenetic signature of salivary gland mucoepidermoid carcinoma in the Serbian population

Nikolic

Čarkić

Dimitrijević

et al. 2018

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

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“…Aberrant CpG island methylation of the promoter region is known to silence some genes as efficiently as mutations or deletions; genome scans for aberrant DNA methylation have shown that up to 10% of CpG islands are methylated in human malignancies (COSTELLO et al, 2000). To this end, involvement of transcriptional silencing of several genes including p16 (SHI et al, 2015;NIKOLIC et al, 2015), MGMT (CHEN et al, 2018), ZNF471 (BHAT et al, 2017) and DAPK1 (JAYAPRAKASH et al, 2017 among others by DNA methylation in cancer development have been established.…”

Section: Discussionmentioning

confidence: 99%

RUNX3 promoter methylation is associated with oral squamous cell carcinoma location

et al. 2021

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The aetiology of OSCC remains unclear, however, aberrant methylation of CpG island promoters of tumor suppressor genes have been identified as contributory developmental pathways in several cancers. The aim of this study was to determine the presence of RUNX3 gene methylation and how its association with patients? demographic variables such as gender, age, histologic class and tumor location could be of diagnostic value for OSCC. Sixty-seven formalin-fixed paraffin-embedded (FFPE) solid tissue blocks of OSCC, and nine blocks of benign oral lesions of epithelial origin retrieved from the archives of the Department of Oral Pathology, University College Hospital, Ibadan, South-West Nigeria were used for the analyses. Frequency of CpG island methylation in the promoter region of RUNX3 was determined by methylation-specific polymerase chain reaction (MSP). Association between gender, age, tumor location, histologic class and promoter methylation in RUNX3 was assessed with Pearson?s ?2 test. Overall, 45% (30/67) of OSCC demonstrated methylation in the RUNX3 promoter indicating a high frequency of methylation of the CpG island promoter region of RUNX3. There was no association between gender, age, histologic class and promoter methylation in RUNX3 (P > 0.05), however a significant association was observed between tumor location and promoter methylation of RUNX3 (P < 0.05). Aberrant methylation of the CpG island promoter region of RUNX3 together with tumor location could therefore be critical in the development and diagnosis of OSCC.

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High frequency of p16 and p14 promoter hypermethylation and marked telomere instability in salivary gland tumors

Cited by 18 publications

References 43 publications

Particulate matter-induced senescence of skin keratinocytes involves oxidative stress-dependent epigenetic modifications

Particulate matter-induced senescence of skin keratinocytes involves oxidative stress-dependent epigenetic modifications

P14 methylation: an epigenetic signature of salivary gland mucoepidermoid carcinoma in the Serbian population

RUNX3 promoter methylation is associated with oral squamous cell carcinoma location

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