The Association and Clinical Significance of CDKN2A Promoter Methylation in Head and Neck Squamous Cell Carcinoma: a Meta-Analysis

Zhou, Chongchang; Shen, Zhisen; Ye, Dong; Li, Qun; Deng, Hongxia; Liu, Huigao; Li, Jinyun

doi:10.1159/000494473

Cited by 47 publications

(35 citation statements)

References 98 publications

(30 reference statements)

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“…Biochemical Genetics (2020) 58:213-244 2017associated with male gender as well as with LN metastasis. Methylated CDKN2A may therefore be a useful marker in diagnosis and prognosis for head and neck cancer (Zhou et al 2018).…”

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confidence: 99%

Epigenetic Modifications in Head and Neck Cancer

et al. 2019

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Head and neck squamous cell carcinoma (HNSCC) is the sixth most common human malignancy in the world, with high mortality and poor prognosis for patients. Among the risk factors are tobacco and alcohol intake, human papilloma virus, and also genetic and epigenetic modifications. Many studies show that epigenetic events play an important role in HNSCC development and progression, including DNA methylation, chromatin remodeling, histone posttranslational covalent modifications, and effects of non-coding RNA. Epigenetic modifications may influence silencing of tumor suppressor genes by promoter hypermethylation, regulate transcription by microRNAs and changes in chromatin structure, or induce genome instability through hypomethylation. Moreover, getting to better understand aberrant patterns of methylation may provide biomarkers for early detection and diagnosis, while knowledge about target genes of microRNAs may improve the therapy of HNSCC and extend overall survival. The aim of this review is to present recent studies which demonstrate the role of epigenetic regulation in the development of HNSCC.

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confidence: 99%

Epigenetic Modifications in Head and Neck Cancer

et al. 2019

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“…Suppression of these genes by hypermethylation, and a reduction in their protein abundance, possibly promotes carcinogenesis. Notably cancerous cells often express CDKN2A at low levels mostly, in which through gene methylation [27,28].…”

Section: Discussionmentioning

confidence: 99%

Host proteome linked to HPV E7-mediated specific gene hypermethylation in cancer pathways

Rangsee

Yanatatsaneejit

Pisitkun

et al. 2020

Infect Agents Cancer

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Background: Human papillomavirus (HPV) infection causes around 90% of cervical cancer cases, and cervical cancer is a leading cause of female mortality worldwide. HPV-derived oncoprotein E7 participates in cervical carcinogenesis by inducing aberrant host DNA methylation. However, the targeting specificity of E7 methylation of host genes is not fully understood but is important in the down-regulation of crucial proteins of the hallmark cancer pathways. In this study, we aim to link E7-driven aberrations in the host proteome to corresponding gene promoter hypermethylation events in the hope of providing novel therapeutic targets and biomarkers to indicate the progression of cervical cancer. Methods: HEK293 cells were transfected with pcDNA3.1-E7 plasmid and empty vector and subjected to mass spectrometry-based proteomic analysis. Down-regulated proteins (where relative abundance was determined significant by paired T-test) relevant to cancer pathways were selected as gene candidates for mRNA transcript abundance measurement by qPCR and expression compared with that in SiHa cells (HPV type 16 positive). Methylation Specific PCR was used to determine promoter hypermethylation in genes downregulated in both SiHa and transfected HEK293 cell lines. The FunRich and STRING databases were used for identification of potential regulatory transcription factors and the proteins interacting with transcription factor gene candidates, respectively. Results: Approximately 400 proteins totally were identified in proteomics analysis. The transcripts of six genes involved in the host immune response and cell proliferation (PTMS, C1QBP, BCAP31, CDKN2A, ZMYM6 and HIST1H1D) were down-regulated, corresponding to proteomic results. Methylation assays showed four gene promoters (PTMS, C1QBP, BCAP31 and CDKN2A) were hypermethylated with 61, 55.5, 70 and 78% increased methylation, respectively. Those four genes can be regulated by the GA-binding protein alpha chain, specificity protein 1 and ETS-like protein-1 transcription factors, as identified from FunRich database predictions. Conclusions: HPV E7 altered the HEK293 proteome, particularly with respect to proteins involved in cell proliferation and host immunity. Down-regulation of these proteins appears to be partly mediated via host DNA methylation. E7 possibly complexes with the transcription factors of its targeting genes and DNMT1, allowing methylation of specific target gene promoters.

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“…In CRC, methylated MLH1 is one of the major epigenetic biomarkers along with other genes involved in the tumor progression and metastasis, such as CDKN2A/p16(INK4A), CDKN2A/p14(ARF), MGMT, TIMP, THBS1 3, and THSD1 (thrombospondin type 1 domain containing 1), identified in genome-wide screening for methylation-silenced genes, along with meta-analysis of clinical data. CDKN2A hypermethylation correlates with tumor progression, metastasis, and overall survival, thus representing a promising diagnostic and prognostic biomarker in HNSCC (head and neck squamous cell carcinoma) [58].…”

Section: Dna Methylation In the Control Of Tumor Suppressor Genesmentioning

confidence: 99%

Multifaceted Roles of DNA Methylation in Neoplastic Transformation, from Tumor Suppressors to EMT and Metastasis

Casalino

Verde

2020

Genes

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Among the major mechanisms involved in tumorigenesis, DNA methylation is an important epigenetic modification impacting both genomic stability and gene expression. Methylation of promoter-proximal CpG islands (CGIs) and transcriptional silencing of tumor suppressors represent the best characterized epigenetic changes in neoplastic cells. The global cancer-associated effects of DNA hypomethylation influence chromatin architecture and reactivation of repetitive elements. Moreover, recent analyses of cancer cell methylomes highlight the role of the DNA hypomethylation of super-enhancer regions critically controlling the expression of key oncogenic players. We will first summarize some basic aspects of DNA methylation in tumorigenesis, along with the role of dysregulated DNA methyltransferases and TET (Ten-Eleven Translocation)-family methylcytosine dioxygenases. We will then examine the potential contribution of epimutations to causality and heritability of cancer. By reviewing some representative genes subjected to hypermethylation-mediated silencing, we will survey their oncosuppressor functions and roles as biomarkers in various types of cancer. Epithelial-to-mesenchymal transition (EMT) and the gain of stem-like properties are critically involved in cancer cell dissemination, metastasis, and therapeutic resistance. However, the driver vs passenger roles of epigenetic changes, such as DNA methylation in EMT, are still poorly understood. Therefore, we will focus our attention on several aspects of DNA methylation in control of EMT and metastasis suppressors, including both protein-coding and noncoding genes.

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The Association and Clinical Significance of CDKN2A Promoter Methylation in Head and Neck Squamous Cell Carcinoma: a Meta-Analysis

Cited by 47 publications

References 98 publications

Epigenetic Modifications in Head and Neck Cancer

Epigenetic Modifications in Head and Neck Cancer

Host proteome linked to HPV E7-mediated specific gene hypermethylation in cancer pathways

Multifaceted Roles of DNA Methylation in Neoplastic Transformation, from Tumor Suppressors to EMT and Metastasis

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