title: Fibulin-1 is epigenetically down-regulated and related with bladder cancer recurrence.
abstract: BACKGROUND
  Bladder cancer is one of the most common cancers worldwide. Fibulin-1, a multi-functional extracellular matrix protein, has been demonstrated to be involved in many kinds of cancers, while its function in bladder cancer remains unclear. So here we investigated the expression and function of fibulin-1 in Bladder cancer.
  
  
  METHODS
  We used real-time PCR, Western blot analysis and immunohistochemistry to determine the expression of fibulin-1 in Bladder cancer cells and patient tissues respectively. Methylation-specific PCR and quantitative sequencing were used to examine the methylation status of FBLN1 gene promoter. Eukaryotic expression plasmid and lentiviral vector were used to overexpress fibulin-1 in Bladder cancer cells 5637, HT-1376 to investigate its function in vitro and in vivo.
  
  
  RESULTS
  We identified that fibulin-1 was significantly down-regulated in bladder cancer, and its dysregulation was associated with non-muscle-invasive bladder cancer (NMIBC) grade and recurrence. The promoter region of FBLN1 was generally methylated in bladder cancer cell lines and tissues, further investigation in patient tissues showed that the methylation status was associated with the fibulin-1 expression. Overexpression of fibulin-1 significantly suppressed tumor growth, induced tumor cell apoptosis, decreased cell motility, and inhibited angiogenesis in cultured bladder cancer cells and xenograft tumor in nude mice.
  
  
  CONCLUSIONS
  Altogether, our results indicated that fibulin-1 expression is associated with NMIBC grade and recurrence, it is epigenetically down-regulated and functions as a tumor suppressor gene and angiogenesis inhibitor in bladder cancer.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.forename: Ding
authors.initials: D
authors.lastname: Xia
authors.forename: Gan
authors.initials: G
authors.lastname: Yu
authors.forename: Weimin
authors.initials: W
authors.lastname: Yao
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Haibing
authors.initials: H
authors.lastname: Xiao
authors.forename: Bin
authors.initials: B
authors.lastname: Lang
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Guo
authors.forename: Wei
authors.initials: W
authors.lastname: Guan
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. xuhua@mail.hust.edu.cn.
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.forename: Jihong
authors.initials: J
authors.lastname: Liu
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhangqun
authors.initials: Z
authors.lastname: Ye
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019175:DNA Methylation; D004195:Disease Models, Animal; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D002135:Calcium-Binding Proteins; C060820:fibulin