The over expression of long non-coding RNA ANRIL promotes epithelial-mesenchymal transition by activating the ATM-E2F1 signaling pathway in pancreatic cancer: An in vivo and in vitro study
Authors: Yan-Ling Chen
Jiang-Zhi Chen
Yao-Dong Wang
Shi Chen
Yi-Feng Tian
Fu-Nan Qiu
Jia-Qiang Zhang
Mao-Lin Yan
Cheng-Hong Peng
Hui-Xing Chen
Journal: International Journal of Biological Macromolecules (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Epithelial-mesenchymal transition and rat model; Long non-coding RNA ANRIL; Pancreatic cancer; the ATM-E2F1 signaling pathway.
Affiliations: Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fujian Medical University, Fuzhou 350001, P.R. China; Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China; Research Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China., Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China; Research Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China., Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China; Research Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Department of Hepatobiliary Surgery, Union Hospital, Fujian Medical University, Fuzhou 350001, PR China., Department of Hepatobiliary Surgery, Union Hospital, Fujian Medical University, Fuzhou 350001, PR China., Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fujian Medical University, Fuzhou 350001, P.R. China., Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fujian Medical University, Fuzhou 350001, P.R. China. Electronic address: .

Abstract:  This study aims to investigate the roles of lncRNA ANRIL in epithelial-mesenchymal transition (EMT) by regulating the ATM-E2F1 signaling pathway in pancreatic cancer (PC). PC rat models were established and ANRIL overexpression and interference plasmids were transfected. The expression of ANRIL, EMT markers (E-cadherin, N-cadherin and Vimentin) and ATM-E2F1 signaling pathway-related proteins (ATM, E2F1, INK4A, INK4B and ARF) were detected. Small molecule drugs were applied to activate and inhibit the ATM-E2F1 signaling pathway. Transwell assay and the scratch test were adopted to detect cell invasion and migration abilities. ANRIL expression in the PC cells was higher than in normal pancreatic duct epithelial cells. In the PC rat models and PC cells, ANRIL interference promoted the expressions of INK4B, INK4A, ARF and E-cadherin, while reduced N-cadherin and Vimentin expression. Over-expressed ANRIL decreased the expression of INK4B, INK4A, ARF and E-cadherin, but raised N-cadherin and Vimentin expressions. By inhibiting the ATM-E2F1 signaling pathway in PC cells, E-cadherin expression increased but N-cadherin and Vimentin expressions decreased. After ANRIL was silenced or the ATM-E2F1 signaling pathway inhibited, PC cell migration and invasion abilities were decreased. In conclusion, over-expression of lncRNA ANRIL can promote EMT of PC cells by activating the ATM-E2F1 signaling pathway. 

Retracted: No

PubPeer comments:
 Fig 9. One of the protein blobs is quite distinctive in shape.  , 
 Fig 11 A,C.  Invasion of human PC cell lines Note: A, cell invasion after ANRIL and ATM overexpression or interference in PANC1 cell line; B, statistical results of PANC1 cell line invasion; C, cell invasion after ANRIL and ATM overexpression or interference in Miapaca II cell line . A panel seems to be repeated for both cell lines.  , 
 Dear Hoya Camphorifoliauff0c Thank you for your attention to our research. We have found the mistakes in this article which was caused by the wrong typesetting. After careful check our raw data, we found that there was no problem.u00a0We have contacted the editor and provided the correct figure in July, but the editor has not replied yet, u00a0more positive contact is under way. Yours sincerely. , 
 Dear Hoya Camphorifoliauff0c Thank you for your attention to our research. We have found the mistakes in this article which was caused by the wrong typesetting. After careful check our raw data, we found that there was no problem.u00a0We have contacted the editor and provided the correct figure in July, but the editor has not replied yet, u00a0more positive contact is under way. Yours sincerely. , 
 #4 It is very unclear to me how the concern illustrated in #1 could occur during the final stages of manuscript preparation. Could the authors please provide the uncropped original scan here to reassure readers about the authenticity of the data? Green arrow below indicates another possible concern. *** Enhanced contrast  ,