ArticleClinical and experimental otorhinolaryngology2022
Induction of the BRAFV600E Mutation in Thyroid Cells Leads to Frequent Hypermethylation.
Article in Clinical and experimental otorhinolaryngology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 8 citations in OpenAlex.
- CHD4 and NOX4 expression in thyroid tumor tissues.Exploration of targeted anti-tumor therapy · 2026Article
- Anaplastic thyroid cancer: Genetic roles, targeted therapy, and immunotherapy.Genes & diseases · 2025Review
- Article
- Effect of long-stranded non-coding RNA-BANCR on the progression of thyroid papillary carcinoma and its mechanism.Discover oncology · 2025Article
- High aggressiveness of papillary thyroid cancer: from clinical evidence to regulatory cellular networks.Cell death discovery · 2024Review
- BRAFMedical journal of the Islamic Republic of Iran · 2024Article
- Mitochondrial Ribosomal Protein L14 Promotes Cell Growth and Invasion by Modulating Reactive Oxygen Species in Thyroid Cancer.Clinical and experimental otorhinolaryngology · 2023Article
- Association of DNA Promoter Methylation andCurrent oncology (Toronto, Ont.) · 2023Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
objectivesThe BRAFV600E mutation is a major driver mutation in papillary thyroid cancer. The aim of this study was to elucidate the correlation between DNA methylation and gene expression changes induced by the BRAFV600E mutation in thyroid cells.
methodsWe used Nthy/BRAF cell lines generated by transfection of Nthy/ori cells with the wild-type BRAF gene (Nthy/WT cells) and the V600E mutant-type BRAF gene (Nthy/V600E cells). We performed gene expression microarray and DNA methylation array analyses for Nthy/WT and Nthy/V600E cells. Two types of array data were integrated to identify inverse correlations between methylation and gene expression. The results were verified in silico using data from The Cancer Genome Atlas (TCGA) and in vivo through pyrosequencing and quantitative real-time polymerase chain reaction (qRT-PCR).
resultsIn the Nthy/V600E cells, 199,821 probes were significantly hypermethylated, and 697 genes showed a "hypermethylation-downregulation" pattern in Nthy/V600E. Tumor suppressor genes and apoptosis-related genes were included. In total, 66,446 probes were significantly hypomethylated, and 227 genes showed a "hypomethylation-upregulation" pattern in Nthy/V600E cells. Protooncogenes and developmental protein-coding genes were included. In the TCGA analysis, 491/697 (70.44%) genes showed a hypermethylation-downregulation pattern, and 153/227 (67.40%) genes showed a hypomethylation-upregulation pattern. Ten selected genes showed a similar methylation-gene expression pattern in pyrosequencing and qRT-PCR.
conclusionInduction of the BRAFV600E mutation in thyroid cells led to frequent hypermethylation. Anticancer genes, such as those involved in tumor suppression or apoptosis, were downregulated by upstream hypermethylation, whereas carcinogenic genes, such as protooncogenes, were upregulated by hypomethylation. Our results suggest that the BRAFV600E mutation in thyroid cells modulates DNA methylation and results in cancer-related gene expression.
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