Related Experiment Video

Updated: Apr 12, 2026

Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics
11:28

Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics

Published on: May 11, 2016

9.1K

Analysis of DNA methylation and gene expression in radiation-resistant head and neck tumors

Xiaofei Chen1, Liang Liu, Jade Mims

  • 1a Section on Molecular Medicine; Department of Internal Medicine; Wake Forest School of Medicine ; Winston-Salem , NC , USA.

Epigenetics
|May 12, 2015
PubMed

Insights

Global DNA methylation increases in head and neck squamous cell cancer (HNSCC) cells resistant to radiation therapy. This epigenetic change, particularly in cell cycle regulation genes like CCND2, may serve as a biomarker for radiation resistance in HNSCC.

Area of Science:

  • Oncology
  • Epigenetics
  • Cancer Genomics

Background:

  • Radiation therapy resistance is a major challenge in treating head and neck squamous cell cancer (HNSCC).
  • Epigenetic alterations, specifically DNA methylation changes, are implicated in the development of treatment resistance.

Purpose of the Study:

  • To investigate DNA methylation patterns associated with radiation resistance in HNSCC.
  • To identify potential biomarkers and therapeutic targets for overcoming radiation resistance in HNSCC.

Main Methods:

  • Analysis of DNA methylation using the Illumina HumanMethylation450 BeadChip in matched radiation-sensitive (SCC-61) and radiation-resistant (rSCC-61) HNSCC cell lines.
  • Integration of DNA methylation data with microarray gene expression data.
  • Pathway analysis (Ingenuity Pathway Analysis) and validation studies, including treatment with a DNA hypomethylating agent (5-aza-2'deoxycitidine).
  • Analysis of The Cancer Genome Atlas (TCGA) HNSCC dataset.

Main Results:

  • Radiation-resistant HNSCC cells (rSCC-61) exhibited significantly increased global DNA methylation compared to radiation-sensitive cells (SCC-61).
  • 84 differentially methylated and expressed genes were identified, with pathways like ILK signaling, glucocorticoid receptor signaling, and cell cycle regulation highlighted.
  • The cell cycle regulator CCND2 was found to be hypermethylated and downregulated in resistant cells, with its expression restored by a hypomethylating agent.
  • TCGA data confirmed increased methylation in radiation-resistant HNSCC tumors.

Conclusions:

  • Global DNA methylation status serves as a potential biomarker for radiation resistance in HNSCC.
  • Targeted manipulation of DNA methylation could enhance radiation therapy response in HNSCC patients.
  • CCND2 and its regulation via DNA methylation represent a potential therapeutic avenue.
Keywords:
5-Aza, 5-aza-2′deoxycitidineAKT, Protein kinase BAraC, Cytosine arabinosideCCNA1, Cyclin A1CCND2, Cyclin D2CDK4, Cyclin-dependent kinase 4CDKN1A, Cyclin-dependent kinase inhibitor 1A (p21, Cip1)DNA methylationDNMT, DNA methyltransferaseEIF2AK2, Eukaryotic translation initiation factor 2-αkinase 2FASN, Fatty acid synthaseGSK-3, Glycogen synthase kinase 3Gene expressionHM450, HumanMethylation450HNSCC, Head and neck squamous cell cancerHead and neck squamous cell cancer (HNSCC)IGFBP3, Insulin-like growth factor-binding protein 3ILK, Integrin linked kinaseIPA, Ingenuity pathway analysisIRF1, Interferon regulatory factor 1KLF4, Kruppel-like factor 4KRT19, Keratin 19, LIPG, Endothelial lipaseLXR, Liver X receptorMGMT, O6-methylguanine DNA methyltransferaseNFATC2, Nuclear factor of activated t-cells cytoplasmic 2PCNA, Proliferating cell nuclear antigenPTEN, Phosphatase and tensin homologRXR, Retinoid X receptorRadiation resistanceSAM, S-AdenosylmethionineSOCS3, Suppressor of cytokine signaling 3STAT1, Signal transducers and activators of transcription 1TCGA, The Cancer Genome AtlasThe Cancer Genome Atlas (TCGA)VHL, Von Hippel–Lindau tumor suppressordmCpG, differentially methylated CpGhTERT, human telomerase reverse transcriptase

More Related Videos

Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment07:29

Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment

Published on: April 22, 2019

12.5K
Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma06:11

Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma

Published on: April 20, 2018

10.4K

Related Concept Videos