FOXM1 induces a global methylation signature that mimics the cancer epigenome in head and neck squamous cell carcinoma
| Autor: | Emilios Gemenetzidis, Iain Hutchison, Ahmad Waseem, Muy-Teck Teh, Adiam W. Bahta, Deeviyaben Patel, Rameez Tariq, Ayesha Nadir |
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| Rok vydání: | 2011 |
| Předmět: |
Epigenomics
Methyltransferase lcsh:Medicine Gene Expression medicine.disease_cause HELLS DNA Methyltransferase 3A 0302 clinical medicine DNA (Cytosine-5-)-Methyltransferases lcsh:Science Promoter Regions Genetic Cells Cultured 0303 health sciences Multidisciplinary Reverse Transcriptase Polymerase Chain Reaction Forkhead Transcription Factors Genomics Head and Neck Tumors Clinical Laboratory Sciences 3. Good health Oncology Head and Neck Neoplasms 030220 oncology & carcinogenesis DNA methylation Carcinoma Squamous Cell Medicine RNA Interference Epigenetics Research Article DNA (Cytosine-5-)-Methyltransferase 1 Immunoblotting Biology 03 medical and health sciences Diagnostic Medicine Cell Line Tumor medicine Genetics Cancer Detection and Diagnosis Humans Cyclin-Dependent Kinase Inhibitor p16 030304 developmental biology Gene Expression Profiling lcsh:R Forkhead Box Protein M1 DNA Helicases Cancers and Neoplasms DNA Methylation medicine.disease Molecular biology Head and neck squamous-cell carcinoma FOXM1 Cancer research lcsh:Q Carcinogenesis |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 3, p e34329 (2012) |
| ISSN: | 1932-6203 |
| Popis: | The oncogene FOXM1 has been implicated in all major types of human cancer. We recently showed that aberrant FOXM1 expression causes stem cell compartment expansion resulting in the initiation of hyperplasia. We have previously shown that FOXM1 regulates HELLS, a SNF2/helicase involved in DNA methylation, implicating FOXM1 in epigenetic regulation. Here, we have demonstrated using primary normal human oral keratinocytes (NOK) that upregulation of FOXM1 suppressed the tumour suppressor gene p16(INK4A) (CDKN2A) through promoter hypermethylation. Knockdown of HELLS using siRNA re-activated the mRNA expression of p16(INK4A) and concomitant downregulation of two DNA methyltransferases DNMT1 and DNMT3B. The dose-dependent upregulation of endogenous FOXM1 (isoform B) expression during tumour progression across a panel of normal primary NOK strains (n = 8), dysplasias (n = 5) and head and neck squamous cell carcinoma (HNSCC) cell lines (n = 11) correlated positively with endogenous expressions of HELLS, BMI1, DNMT1 and DNMT3B and negatively with p16(INK4A) and involucrin. Bisulfite modification and methylation-specific promoter analysis using absolute quantitative PCR (MS-qPCR) showed that upregulation of FOXM1 significantly induced p16(INK4A) promoter hypermethylation (10-fold, P |
| Databáze: | OpenAIRE |
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