单位:[1]Huazhong Univ Sci & Technol,Tongji Med Coll,Tongji Hosp,Dept Urol,Wuhan 430030,Peoples R China;华中科技大学同济医学院附属同济医院外科学系泌尿外科[2]Huazhong Univ Sci & Technol,Tongji Med Coll,Tongji Hosp,Translat Med Ctr,Wuhan 430030,Peoples R China;华中科技大学同济医学院附属同济医院转化医学中心[3]Univ Calif San Francisco, Dept Urol, San Francisco, CA USA;[4]Univ Calif San Francisco, Helen Diller Comprehens Canc Ctr, San Francisco, CA 94143 USA;[5]Peoples Liberat Army Gen Hosp, Mil Postgrad Med Coll, Dept Urol, Beijing 100853, Peoples R China;[6]Macao Polytech Inst, Sch Hlth Sci, Cathedral Parish, Peoples R China
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.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31072238, 31172441, 81170650, 81402087]; National Major Scientific and Technological Special Project for "Significant New Drugs Development" [2012ZX09303018]
第一作者单位:[2]Huazhong Univ Sci & Technol,Tongji Med Coll,Tongji Hosp,Translat Med Ctr,Wuhan 430030,Peoples R China;
通讯作者:
通讯机构:[1]Huazhong Univ Sci & Technol,Tongji Med Coll,Tongji Hosp,Dept Urol,Wuhan 430030,Peoples R China;
推荐引用方式(GB/T 7714):
Xiao Wei,Wang Ji,Li Heng,et al.Fibulin-1 is epigenetically down-regulated and related with bladder cancer recurrence[J].BMC CANCER.2014,14:677.doi:10.1186/1471-2407-14-677.
APA:
Xiao, Wei,Wang, Ji,Li, Heng,Xia, Ding,Yu, Gan...&Ye, Zhangqun.(2014).Fibulin-1 is epigenetically down-regulated and related with bladder cancer recurrence.BMC CANCER,14,
MLA:
Xiao, Wei,et al."Fibulin-1 is epigenetically down-regulated and related with bladder cancer recurrence".BMC CANCER 14.(2014):677