Epigenetic mediated zinc finger protein 671 downregulation promotes cell proliferation and tumorigenicity in nasopharyngeal carcinoma by inhibiting cell cycle arrest.
BACKGROUND
Epigenetic abnormalities play important roles in nasopharyngeal cancer (NPC), however, the epigenetic changes associated with abnormal cell proliferation remain unclear.


METHODS
We detected epigenetic change of ZNF671 in NPC tissues and cell lines by bisulfite pyrosequencing. We evaluated zinc finger protein 671 (ZNF671) expression in NPC cell lines and clinical tissues using real-time PCR and western blotting. Then, we established NPC cell lines that stably overexpressed ZNF671 and knocked down ZNF671 expression to explore its function in NPC in vitro and in vivo. Additionally, we investigated the potential mechanism of ZNF671 by identifying the mitotic spindle and G2/M checkpoint pathways pathway downstream genes using gene set enrichment analysis, flow cytometry and western blotting.


RESULTS
ZNF671 was hypermethylated in NPC tissues and cell lines. The mRNA and protein expression of ZNF671 was down-regulated in NPC tissues and cell lines and the mRNA expression could be upregulated after the demethylation agent 5-aza-2'-deoxycytidine treatment. Overexpression of ZNF671 suppressed NPC cell proliferation and colony formation in vitro; silencing ZNF671 using a siRNA had the opposite effects. Additionally, overexpression of ZNF671 reduced the tumorigenicity of NPC cells in xenograft model in vivo. The mechanism study determined that overexpressing ZNF671 induced S phase arrest in NPC cells by upregulating p21 and downregulating cyclin D1 and c-myc.


CONCLUSIONS
Epigenetic mediated zinc finger protein 671 downregulation promotes cell proliferation and enhances tumorigenicity by inhibiting cell cycle arrest in NPC, which may represent a novel potential therapeutic target.
['Zhang|Jian|J|', 'Wen|Xin|X|', 'Liu|Na|N|', 'Li|Ying-Qin|YQ|', 'Tang|Xin-Ran|XR|', 'Wang|Ya-Qin|YQ|', 'He|Qing-Mei|QM|', 'Yang|Xiao-Jing|XJ|', 'Zhang|Pan-Pan|PP|', 'Ma|Jun|J|', 'Sun|Ying|Y|']
D000818:Animals D002277:Carcinoma D059447:Cell Cycle Checkpoints D045744:Cell Line, Tumor D049109:Cell Proliferation D019175:DNA Methylation D015536:Down-Regulation D044127:Epigenesis, Genetic D015972:Gene Expression Regulation, Neoplastic D053263:Gene Regulatory Networks D059014:High-Throughput Nucleotide Sequencing D006801:Humans D051379:Mice D000077274:Nasopharyngeal Carcinoma D009303:Nasopharyngeal Neoplasms D009368:Neoplasm Transplantation D017422:Sequence Analysis, DNA D025521:Tumor Suppressor Proteins
Proliferation Tumorigenicity Nasopharyngeal carcinoma ZNF671 Hypermethylation