title: c-Myc inhibits TP53INP1 expression via promoter methylation in esophageal carcinoma.
abstract: Tumor protein p53-induced nuclear protein 1 (TP53INP1) is a well known stress-induced protein that plays a role in both cell cycle arrest and p53-mediated apoptosis. Loss of TP53INP1 expression has been reported in human melanoma, breast carcinoma, and gastric cancer. However, TP53INP1 expression and its regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remain unclear. Our findings are in agreement with previous reports in that the expression of TP53INP1 was downregulated in 28% (10/36 cases) of ESCC lesions, and this was accompanied by significant promoter methylation. Overexpression of TP53INP1 induced G1 cell cycle arrest and increased apoptosis in ESCC cell lines (EC-1, EC-109, EC-9706). Furthermore, our study showed that the oncoprotein c-Myc bound to the core promoter of TP53INP1 and recruited DNA methyltransferase 3A to methylate the local promoter region, leading to the inhibition of TP53INP1 expression. Our findings revealed that TP53INP1 is a tumor suppressor in ESCC and that c-Myc-mediated DNA methylation-associated silencing of TP53INP1 contributed to the pathogenesis of human ESCC.
authors.affiliation: Department of Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, PR China.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Weng
authors.forename: Qinyuan
authors.initials: Q
authors.lastname: Yang
authors.forename: Miaolong
authors.initials: M
authors.lastname: Huang
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Qiao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xie
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Yu
authors.forename: An
authors.initials: A
authors.lastname: jing
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018899:CpG Islands; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C000717967:DNMT3A protein, human; D006360:Heat-Shock Proteins; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C429767:TP53INP1 protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A