title: Effects of DNA methyltransferase 1 inhibition on esophageal squamous cell carcinoma.
abstract: To explore the role of DNA methyltransferase 1 (DNMT1) in esophageal squamous cell carcinoma (ESCC) and the potential of DNMT1-targeted small interfering RNA as ESCC therapy, we examined expression changes of DNMT1 in ESCC and investigated the effect of DNMT1 knockdown by RNA interference in a human ESCC cell line, KYSE30. DNMT1 messenger RNA was over-expressed in seven out of 12 ESCC samples, and the percentage of cells expressing DNMT1 was significantly higher in ESCC tissues compared with paired non-cancerous tissues. DNMT1 protein levels correlated with lymph node metastasis, but exhibited no correlation with sex, age, tumor site, or tumor differentiation. Knockdown of DNMT1 in KYSE30 cells using RNA interference resulted in a reduction of promoter methylation and re-expression of methyl-guanine methyl-transferase and retinoic acid receptors beta, inhibition of cell proliferation/viability and induction of cell apoptosis. These results indicate that DNMT1 over-expression is involved in ESCC and correlated with lymph node metastasis. Knockdown of DNMT1 led to promoter demethylation and re-expression of several tumor suppressor genes thereby inhibiting cell proliferation/viability and inducing cell apoptosis.
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital-Capital Medical University, Yongan Road 95, Beijing, China.
authors.forename: Shu-Lei
authors.initials: SL
authors.lastname: Zhao
authors.forename: Sheng-Tao
authors.initials: ST
authors.lastname: Zhu
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Hao
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Shu-Tian
authors.initials: ST
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D000091363:Protocadherins; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015820:Cadherins; C438603:PCDH10 protein, human; D000091363:Protocadherins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C482860:UCHL1 protein, human; C082925:retinoic acid receptor beta; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D019853:O(6)-Methylguanine-DNA Methyltransferase; D043222:Ubiquitin Thiolesterase