title: Short hairpin RNA targeting FOXQ1 inhibits invasion and metastasis via the reversal of epithelial-mesenchymal transition in bladder cancer.
abstract: 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.
authors: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, P.R. China.
authors: Zhaohui
authors: Z
authors: Zhu
authors: Zhineng
authors: Z
authors: Zhu
authors: Zili
authors: Z
authors: Pang
authors: Yifei
authors: Y
authors: Xing
authors: Feng
authors: F
authors: Wan
authors: Dongyang
authors: D
authors: Lan
authors: Haipeng
authors: H
authors: Wang
mesh_terms: D000368:Aged; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D002470:Cell Survival; D058750:Epithelial-Mesenchymal Transition; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology; D014746:Vimentin / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C484579:FOXQ1 protein, human; D051858:Forkhead Transcription Factors; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D014746:Vimentin