Methylation of ZNF331 Promotes Cell Invasion and Migration in Human Esophageal Cancer.
Loss of zinc-finger protein 331 (ZNF331) expression was reported in gastric cancer. To explore the regulation of expression and the function of ZNF331 in human esophageal cancer, 11 esophageal cancer cell lines, 7 cases of normal esophageal mucosa and 99 cases of primary esophageal squamous cancer were employed. Methylation specific PCR, semi-quantitive reverse transcriptase PCR, immunohistochemistry, western blot, flow cytometry, wound healing and transwell assay were used. The expression of ZNF331 was silenced by promoter region hypermethylation in 8 of 11 esophageal cancer cell lines. 56.5% (56/99) of primary human esophageal cancer was methylated, but no methylation was found in 7 cases of normal esophageal mucosa. The expression of ZNF331 was reduced in human primary esophageal cancer and reduced expression was associated with promoter region methylation. No significant change was found in cell viability (P>0.05) and cell phase distribution (P>0.05) before and after re-expression in KYSE150 and KYSE410 cells. The migration was suppressed by ZNF331 apparently under wound healing experiment. Re-expression of ZNF331 expression significantly suppressed cell migration and invasion (P<0.05). In conclusion, ZNF331 is frequently methylated in human esophageal cancer. The expression of ZNF331 is regulated by promoter region methylation. ZNF331 may suppress esophageal cancer metastasis.
Suzhen
S
Jiang
Enqiang
E
Linghu
Qimin
Q
Zhan
Weidong
W
Han
Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing, China. mzguo1@gmail.com.
Mingzhou
M
Guo
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; C403666:ZNF331 protein, human