Fibulin-1 is epigenetically down-regulated and related with bladder cancer recurrence

Wei Xiao, Ji Wang, Heng Li, Ding Xia, Gan Yu, Weimin Yao, Yang Yang, Haibing Xiao, Bin Lang, Xin Ma, Xiaolin Guo, Wei Guan, Hua Xu, Jihong Liu, Xu Zhang, Zhangqun Ye

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish (US)
Article number677
JournalBMC Cancer
Volume14
Issue number1
DOIs
StatePublished - Sep 18 2014

Keywords

  • Bladder cancer
  • Cancer recurrence
  • Fibulin-1
  • Promoter hypermethylation
  • Tumor suppressor gene

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