Open AccessThe Role of G9a in Tumorigenesis in Head and Neck Cancer
Author(s) -
Tan ChingTing,
Ko JenqYuh,
Tsai HungHuey
Publication year - 2012
Publication title -
otolaryngology–head and neck surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.232
H-Index - 121
eISSN - 1097-6817
pISSN - 0194-5998
DOI - 10.1177/0194599812451426a184
Subject(s) - head and neck squamous cell carcinoma , carcinogenesis , cancer research , histone methyltransferase , gene knockdown , histone h3 , cell growth , biology , cancer , small hairpin rna , epigenetics , head and neck cancer , cell culture , gene , biochemistry , genetics
Objective Head and neck squamous cell carcinoma (HNSCC) represents a major worldwide health problem with patients, exhibiting a 5‐year average survival rate lower than 50%. G9a is a histone methyltransferase (HMTase) for histone H3 lysine 9 dimethylation (H3K9me2), and it was reported that G9a‐mediated H3K9me2 aberrantly repressed tumor suppressor genes in many cancers. However, the mechanistic understanding of the role of G9a in HNSCC progression remains largely unknown. Method IHC of patients’ tissues were performed. RT‐PCR, western blot, cell viability assay, and anchorage‐independent growth analysis of HNSCC cells were performed. Age‐matched NOD‐SCID mice were used to establish the mouse model for tumorigenesis. Microarray analysis was scanned with the AffymetriGeneChip scanner to evaluate the signal pathway regulated by G9a. Results The results revealed that mRNA expression level of G9a was higher in tumors compared with normal parts. G9a was over‐expressed in cancerous specimens compared with mucosa. Inhibited G9a expression by shRNA or treated G9a enzymatic activity inhibitor BIX‐01294 in HNSCC cells, the results showed that both can significantly inhibit HNSCC cell growth and anchorage‐independent growth. The in vivo animal model also revealed that G9a knockdown would decrease tumor growth. We discovered that DUSP4 was upregulated in G9a‐downregulated HNSCC cells and the expression level of phospho‐ERK was inhibited. DUSP4 expression could also be inhibited after treatment with BIX‐01294 in HNSCC cells. Conclusion Our findings suggested that G9a possessed strong oncogenic properties and correlated with sustained malignant phenotype. Inhibition of G9a expression could suppress HNSCC cells growth and in vivo tumorigenecity.