Short hairpin RNA targeting FOXQ1 inhibits invasion and metastasis via the reversal of epithelial-mesenchymal transition in bladder cancer.
Short hairpin RNA targeting FOXQ1 inhibits invasion and metastasis via the reversal of epithelial-mesenchymal transition in bladder cancer.
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DOI：
10.3892/ijo.2013.1807
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发表时间：
2013-04
影响因子：
5.2
通讯作者：
Zhao-hui Zhu;Zhi-neng Zhu;Zi-li Pang;Y. Xing;Feng Wan;Dong-yang Lan;Hai-peng Wang
中科院分区：
文献类型：
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作者：
Zhao-hui Zhu;Zhi-neng Zhu;Zi-li Pang;Y. Xing;Feng Wan;Dong-yang Lan;Hai-peng Wang
上皮-间质转化（EMT）促进了肿瘤的侵袭和转移，然而，协调这一过程的整合机制尚不完全清楚。在这项研究中，我们确定了叉头转录因子FOXQ 1在调节膀胱癌EMT中的关键功能作用。采用RT-PCR、Western blot和免疫组织化学方法，对65例膀胱移行细胞癌（BTCC）标本中FOXQ 1、TGF-β1和EMT标志物E-cadherin、Vimentin的表达进行初步研究。检索结果显示，BTCC中FOXQ 1的表达与E-cadherin呈负相关，与TGF-β1、Vimentin呈正相关（P<0.05）。此外，我们的目的是构建针对FOXQ 1基因的短发夹RNA（shRNA）表达质粒，并使用Lipofectamine 2000将shRNA导入高转移潜能的人膀胱癌T24细胞。RNAi抑制FOXQ 1表达可逆转高侵袭性T24细胞的EMT过程，并伴有E-cadherin表达上调和Vimentin表达缺失（P<0.05）。siRNA抑制FOXQ 1表达后，T24细胞呈鹅卵石样表型，细胞运动能力和侵袭能力明显降低（P<0.05）。结论：FOXQ 1可能是一种新的EMT诱导转录因子，通过调控E-cadherin的表达和癌细胞的侵袭性，以转录因子FOXQ 1为靶点，可作为肿瘤治疗的新策略。
The epithelial-mesenchymal transition (EMT) promotes cancer invasion and metastasis, however, the integrative mechanisms that coordinate the process are incompletely understood. In this study, we defined a pivotal functional role for the Forkhead transcription factor FOXQ1 in regulating EMT in bladder cancer. We initially investigated the expression of FOXQ1, TGF-β1 and EMT biomarkers E-cadherin, Vimentin in 65 cases of bladder transitional cell carcinoma (BTCC) specimens by reverse transcription-polymerase chain reaction (RT-PCR), western blot analysis and immunohistochemistry. Search results indicated that FOXQ1 expression was inversely correlated to E-cadherin, but positively to TGF-β1 and Vimentin in patients with BTCC (P<0.05). Furthermore, we aimed to construct short hairpin RNA (shRNA) expression plasmids against the FOXQ1 gene and transfect shRNAs into high metastatic potential human bladder cancer T24 cells with Lipofectamine 2000. RNAi-mediated suppression of FOXQ1 expression reversed the EMT process accompanied by upregulation of E-cadherin, as well as a loss expression of Vimentin in highly invasive T24 cells (P<0.05). The inhibition of FOXQ1 expression with shRNA vector also led T24 cells to acquire an epithelial cobblestone phenotype, significantly reduced motility and subsequent invasiveness of bladder cancer cells (P<0.05). In conclusion that FOXQ1 may be a novel EMT-inducing transcription factor through controlling the expression of E-cadherin and aggressiveness of cancer cells and targeting the transcription factor FOXQ1 could hence serve as a novel therapeutic strategy for cancer patients.