title: TGFBR3 co-downregulated with GATA3 is associated with methylation of the GATA3 gene in bladder urothelial carcinoma.
abstract: Bladder urothelial carcinoma (BUC) accounts for ∼90% of all cases of bladder cancer. Reduced expression of TGFBR3 has been frequently observed in several types of human cancers. However, little is known about whether expression of TGFBR3 reduced in BUC and the underlying mechanisms. In the present study, we performed quantitative real-time PCR to examine the mRNA expression of TGFBR3 and GATA3, and bisulfite genomic sequencing to evaluate the methylation status in TGFBR3 and GATA3 promoter regions in fresh tumor and the corresponding paracarcinoma tissues from 29 patients with BUC. As a result, the expression of TGFBR3 and GATA3, a transcriptional factor of the TGFBR3 gene, were found to be co-downregulated in BUC. Moreover, our findings indicated that GATA3 promoter methylation was one of the reasons for silencing of GATA3 and TGFBR3 in BUC, albeit TGFBR3 methylation and mutation were not associated with reduced expression of TGFBR3 mRNA in BUC. In summary, our findings suggest that methylation in the GATA3 promoter region may inhibit the expression of GATA3 mRNA, which leads to the reduced expression of TGFBR3 mRNA in BUC.
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Liu
authors.forename: Bo-Xin
authors.initials: BX
authors.lastname: Xue
authors.forename: Zhe
authors.initials: Z
authors.lastname: Lei
authors.forename: Dong-Rong
authors.initials: DR
authors.lastname: Yang
authors.forename: Qing-Chuan
authors.initials: QC
authors.lastname: Zhang
authors.forename: Yu-Xi
authors.initials: YX
authors.lastname: Shan
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation / Q000502:physiology*; D004273:DNA, Neoplasm / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D001743:Urinary Bladder / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: D004273:DNA, Neoplasm; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D011509:Proteoglycans; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan
keywords: GATA3; TGFBR3; bladder urothelial carcinoma; methylation