Fibulin-1 is epigenetically down-regulated and related with bladder cancer recurrence.
Fibulin-1 is epigenetically down-regulated and related with bladder cancer recurrence.
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Fibulin-1 在表观遗传上下调并与膀胱癌复发相关。
DOI：
10.1186/1471-2407-14-677
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发表时间：
2014-09-18
期刊：
影响因子：
3.8
通讯作者：
Ye Z
中科院分区：
文献类型：
--
作者：
Xiao W;Wang J;Li H;Xia D;Yu G;Yao W;Yang Y;Xiao H;Lang B;Ma X;Guo X;Guan W;Xu H;Liu J;Zhang X;Ye Z
膀胱癌是世界上最常见的癌症之一。纤维蛋白-1是一种多功能的细胞外基质蛋白，已被证明与多种肿瘤有关，但其在膀胱癌中的作用尚不清楚。因此，我们研究了纤维蛋白-1在膀胱癌中的表达和功能。采用实时定量聚合酶链式反应、免疫印迹分析和免疫组织化学方法分别检测膀胱癌细胞和患者组织中纤溶酶原激活物-1的表达。采用甲基化特异性聚合酶链式反应和定量测序方法检测FBLN1基因启动子的甲基化状态。利用真核表达载体和慢病毒载体在膀胱癌5637、HT-1376细胞中过表达fiBulin-1，研究其在体内外的功能。我们发现fiblin-1在膀胱癌中显著下调，其异常表达与非肌肉浸润性膀胱癌(NMIBC)的分级和复发有关。FBLN1启动子区域在膀胱癌细胞系和组织中普遍存在甲基化，进一步的研究表明，患者组织中的甲基化状态与fiblin-1的表达有关。在培养的膀胱癌细胞和裸鼠移植瘤中，过表达fiblin-1显著抑制肿瘤生长，诱导肿瘤细胞凋亡，降低细胞活力，抑制血管生成。综上所述，我们的结果表明，fiblin-1的表达与NMIBC的分级和复发有关，它在表观遗传学上下调，在膀胱癌中作为肿瘤抑制基因和血管生成抑制因子发挥作用。本文的在线版本(DOI：10.1186/1471-2407-14-677)包含补充材料，可供授权用户使用。
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. 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. 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. 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. The online version of this article (doi:10.1186/1471-2407-14-677) contains supplementary material, which is available to authorized users.
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影响因子：
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影响因子：
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作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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