title: Reduction of TIP30 in esophageal squamous cell carcinoma cells involves promoter methylation and microRNA-10b.
abstract: TIP30 is a putative tumor suppressor that can promote apoptosis and inhibit angiogenesis. However, the role of TIP30 in esophageal squamous cell carcinoma (ESCC) biology has not been investigated. Immunohistochemistry was used to investigate the expression of TIP30 in 70 ESCC. Hypermethylation of TIP30 was evaluated by the methylation specific PCR (MSP) method in ESCC (tumor and paired adjacent non-tumor tissues). Lost expression of TIP30 was observed in 50 of 70 (71.4%) ESCC. 61.4% (43 of 70) of primary tumors analyzed displayed TIP30 hypermethylation, indicating that this aberrant characteristic is common in ESCC. Moreover, a statistically significant inverse association was found between TIP30 methylation status and expression of the TIP30 protein in tumor tissues (p=0.001). We also found that microRNA-10b (miR-10b) targets a homologous DNA region in the 3'untranslated region of the TIP30 gene and represses its expression at the transcriptional level. Reporter assay with 3'UTR of TIP30 cloned downstream of the luciferase gene showed reduced luciferase activity in the presence of miR-10b, providing strong evidence that miR-10b is a direct regulator of TIP30. These results suggest that TIP30 expression is regulated by promoter methylation and miR-10b in ESCC.
authors.affiliation: Department of Internal Medicine-Oncology, The First Affiliated Hospital, Zhengzhou University, China. Electronic address: dongwenjie200581@126.com.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Dong
authors.affiliation: Department of Gastroenterology, Rui-jin Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ruizhe
authors.initials: R
authors.lastname: Shen
authors.affiliation: Department of Gastroenterology, Rui-jin Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Shidan
authors.initials: S
authors.lastname: Cheng
mesh_terms: D000123:Acetyltransferases / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000556:secondary*; D019175:DNA Methylation / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000556:secondary*; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: C547183:MIRN10 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; D000123:Acetyltransferases; C111246:HTATIP2 protein, human
keywords: ESCC; Hypermethylation; TIP30; miR-10b