Abstract
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.
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