Expression And Biological Roles Of SUZ12 In Head And Neck Squamous Cell Carcinoma

Background: Epigenetic abnormality is a hallmark of human cancer and greatly contributes to cancer initiation and progression.The transcriptional repressors of the polycomb protein complex(Pc G)regulate the targeted genes expression through chromatin modifications.Pc G proteins play critical roles in malignant transformation,tumor metastasis and chemotherapy drug resistance.In brief,two polycomb repressive complexes(PRC1 and PRC2)harbor multiple core members to execute their functions by histone modi cations and in turn induce gene silencing.Suppressor of zest 12(SUZ12)is one of the core component of PRC2,which is essential for PRC2-mediated gene silencing.However,its expression pattern and associated molecular mechanisms underlying head and neck squamous cell carcinoma(HNSCC)initiation and progression remain largely unknown.Here we aimed to investigate the SUZ12 expression and its biological roles in HNSCC.Objectives: To investigate the expression patterns and oncogenic roles of SUZ12 in HNSCC.Methods: 1.Western blot,Immunohistochemical staining(IHC)was used to examine the expression of SUZ12 in HNSCC cell lines and specimens.The associations between SUZ12 and multiple clinicopathological parameters and prognosis were analyzed.2.The cell phenotype was verified by Western blot,MTT,cell migration assay and invasion assay which were used to dissect the roles of SUZ12 in HNSCC cell such as tumor cells proliferation,migration and invasion after short-hairpin RNA-mediated SUZ12 knockdown in vitro.Results: 1.Western blot results confirmed the upregulated SUZ12 expression in the HNSCC cell lines.We evaluated the expression patterns of SUZ12 by IHC in a retrospective cohort of 72 primary HNSCC specimens.In these HNSCC specimens,there were 37(51.39%)high expression,whereas the negative or low expression group in 15 normal counterparts were 12(80.00%).The results indicated aberrant overexpression of SUZ12 in a major fraction of HNSCC samples(p=0.0025).There were significant correlations between SUZ12 expression with cervical lymph nodes metastasis(p <0.05).In a Kaplan-Meier survival analysis,high SUZ12 expression in HNSCC was significantly associated with reduced overall survival(log-rank,p=0.0225)and disease-free survival rate(p=0.0179),suggesting that SUZ12 overexpression associated with adverse prognosis.2.Short-hairpin RNA-mediated SUZ12 knockdown inhibited cell proliferation,migration,invasion and enhanced 5-FU chemosensitivity in HNSCC cells.Conclusion: SUZ12 was aberrantly overexpressed in human HNSCC cell lines and clinical specimens.SUZ12 overexpression is found to be significantly associated with cervical lymph node metastasis,and also significantly associated with patients' reduced survival rate.SUZ12 silencing inhibited cell proliferation,migration and invasion in vitro.This study suggests that aberrantly overexpression of SUZ12 might be associated with human HNSCC initiation and progression,and also establishes SUZ12 as a novel cancer biomarker for diagnosis and prognostic prediction for HNSCC patients.