Targeting epigenetic modulation of cholesterol synthesis as a therapeutic strategy for head and neck squamous cell carcinoma
- Resource Type
- Authors
- Jianjun Zhang; Wantao Chen; Yan Li; Qing Wang; Ming Yan; Xu Wang; Yanjun Wen; Jun Chen; Qin Xu; Xing Xu; Xiaojie Yang; Yan Wei
- Source
- Cell Death and Disease, Vol 12, Iss 5, Pp 1-15 (2021)
Cell Death & Disease
- Subject
- Epigenomics
Male
Cancer Research
Squalene monooxygenase
Immunology
Mice, Nude
macromolecular substances
Transfection
Article
Cellular and Molecular Neuroscience
Mice
Cell Line, Tumor
Gene expression
medicine
Animals
Humans
Epigenetics
Gene
chemistry.chemical_classification
QH573-671
business.industry
Squamous Cell Carcinoma of Head and Neck
EZH2
Cell Biology
Translational research
medicine.disease
Head and neck squamous-cell carcinoma
Cancer metabolism
stomatognathic diseases
Enzyme
Cholesterol
chemistry
Histone methyltransferase
Cancer research
business
Cytology
- Language
- English
- ISSN
- 2041-4889
The histone methyltransferase EZH2 silences gene expression via H3 lysine 27 trimethylation and has been recognized as an important antitumour therapeutic target. However, the clinical application of existing EZH2 inhibitors is not satisfactory for the treatment of solid tumours. To discover novel strategies against head and neck squamous cell carcinoma (HNSCC), we performed genomics, metabolomics and RNA omics studies in HNSCC cells treated with EZH2 inhibitors. It was found that EZH2 inhibitors strongly induced the expression of genes in cholesterol synthesis. Through extensive drug screening we found that inhibition of squalene epoxidase (a key enzyme of endogenous cholesterol synthesis) synergistically increased the squalene content and enhanced the sensitivity of HNSCC cells to EZH2 inhibitors. Our findings provide an experimental and theoretical basis for the development of new combinations of EZH2 inhibitors to treat HNSCC.