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10.3748/wjg.v23.i13.2318 http://scihub22266oqcxt.onion/10.3748/wjg.v23.i13.2318 C5385398!5385398 !28428711     free     free     free Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28428711 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       World+J+Gastroenterol 2017 ; 23 (13 ): 2318-2329 Nephropedia Template TP {{tp|p=28428711 |t=2017. Cullin 4A is associated with epithelial to mesenchymal transition and poor prognosis in perihilar cholangiocarcinoma |pdf=|usr=}}{{28428711 }} gab.com Text Cullin 4A is associated with epithelial to mesenchymal transition and poor prognosis in perihilar cholangiocarcinoma JO: World J Gastroenterol http://www.kidney.de/pget.php?&tw=1&pmid=28428711 #FOAvip AIM: To explore the functional role of cullin 4A (CUL4A), a core subunit of E3 ubiquitin ligase, in perihilar cholangiocarcinoma (PHCC). METHODS: The expression of CUL4A in PHCC cell lines was evaluated by Western blot and quantitative reverse transcription-polymerase chain reaction. Immunohistochemistry (IHC) was adopted to investigate the relationship between CUL4A expression and clinicopathological characteristics of PHCC. Univariate analysis and multivariate regression analysis were performed to analyze the risk factors related to overall survival (OS) and progression-free survival (PFS) of PHCC patients. Wound healing, Transwell and Matrigel assays were utilized to explore the function of CUL4A in PHCC metastasis. Furthermore, expression of epithelial to mesenchymal transition (EMT) markers was verified in cells with CUL4A knockdown or overexpression. The relationship between CUL4A expression and E-cadherin expression was also analyzed by IHC assay. Finally, the role of ZEB1 in regulating CUL4A mediated PHCC was detected by IHC, Western blot, Transwell and Matrigel assays. RESULTS: CUL4A overexpression was detected in PHCC cell lines and clinical specimens. Clinicopathological analysis revealed a close correlation between CUL4A overexpression and tumour differentiation, T, N and TNM stages in PHCC. Kaplan-Meier analysis revealed that high CUL4A expression was correlated with poor OS and PFS of PHCC patients. Univariate analysis identified the following four parameters as risk factors related to OS rate of PHCC: T, N, TNM stages and high CUL4A expression; as well as three related to PFS: N stage, TNM stage and high CUL4A expression. Further multivariate logistic regression analysis identified high CUL4A expression as the only independent prognostic factor for PHCC. Moreover, CUL4A silencing in PHCC cell lines dramatically inhibited metastasis and the EMT. Conversely, CUL4A overexpression promoted these processes. Mechanistically, ZEB1 was discovered to regulate the function of CUL4A in promoting the EMT and metastasis. CONCLUSION: CUL4A is an independent prognostic factor for PHCC, and it can promote the EMT by regulating ZEB1 expression. CUL4A may be a potential therapeutic target for PHCC. Twit Text FOAVip Cullin 4A is associated with epithelial to mesenchymal transition and poor prognosis in perihilar cholangiocarcinoma ????World J Gastroenterol http://www.kidney.de/pget.php?&tw=1&pmid=28428711 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28428711 #FOAvip English Wikipedia <ref>{{Cite pmid|28428711 }}</ref> Cullin 4A is associated with epithelial to mesenchymal transition and poor prognosis in perihilar cholangiocarcinoma #MMPMID28428711 Zhang TJ ; Xue D ; Zhang CD ; Zhang ZD ; Liu QR ; Wang JQ World J Gastroenterol 2017[Apr]; 23 (13 ): 2318-2329 PMID28428711 show ga AIM: To explore the functional role of cullin 4A (CUL4A), a core subunit of E3 ubiquitin ligase, in perihilar cholangiocarcinoma (PHCC). METHODS: The expression of CUL4A in PHCC cell lines was evaluated by Western blot and quantitative reverse transcription-polymerase chain reaction. Immunohistochemistry (IHC) was adopted to investigate the relationship between CUL4A expression and clinicopathological characteristics of PHCC. Univariate analysis and multivariate regression analysis were performed to analyze the risk factors related to overall survival (OS) and progression-free survival (PFS) of PHCC patients. Wound healing, Transwell and Matrigel assays were utilized to explore the function of CUL4A in PHCC metastasis. Furthermore, expression of epithelial to mesenchymal transition (EMT) markers was verified in cells with CUL4A knockdown or overexpression. The relationship between CUL4A expression and E-cadherin expression was also analyzed by IHC assay. Finally, the role of ZEB1 in regulating CUL4A mediated PHCC was detected by IHC, Western blot, Transwell and Matrigel assays. RESULTS: CUL4A overexpression was detected in PHCC cell lines and clinical specimens. Clinicopathological analysis revealed a close correlation between CUL4A overexpression and tumour differentiation, T, N and TNM stages in PHCC. Kaplan-Meier analysis revealed that high CUL4A expression was correlated with poor OS and PFS of PHCC patients. Univariate analysis identified the following four parameters as risk factors related to OS rate of PHCC: T, N, TNM stages and high CUL4A expression; as well as three related to PFS: N stage, TNM stage and high CUL4A expression. Further multivariate logistic regression analysis identified high CUL4A expression as the only independent prognostic factor for PHCC. Moreover, CUL4A silencing in PHCC cell lines dramatically inhibited metastasis and the EMT. Conversely, CUL4A overexpression promoted these processes. Mechanistically, ZEB1 was discovered to regulate the function of CUL4A in promoting the EMT and metastasis. CONCLUSION: CUL4A is an independent prognostic factor for PHCC, and it can promote the EMT by regulating ZEB1 expression. CUL4A may be a potential therapeutic target for PHCC. |*Epithelial-Mesenchymal Transition [MESH] |Bile Duct Neoplasms/*metabolism/mortality/pathology [MESH] |Bile Ducts/pathology [MESH] |Cell Line [MESH] |Cell Movement [MESH] |Cullin Proteins/*metabolism [MESH] |Gene Expression Regulation, Neoplastic [MESH] |Humans [MESH] |Klatskin Tumor/*metabolism/mortality/pathology [MESH] |Neoplasm Metastasis [MESH]Cullin 4A is associated with epithelial to mesenchymal transition and (epmc).pdf DeepDyve Pubget Overpricing