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.
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.
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.
Shi
S
Chen
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.
Jia-Qiang
JQ
Zhang
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.
Jiang-Zhi
JZ
Chen
Department of Hepatobiliary Surgery, Union Hospital, Fujian Medical University, Fuzhou 350001, PR China.
Hui-Xing
HX
Chen
Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fujian Medical University, Fuzhou 350001, P.R. China.
Fu-Nan
FN
Qiu
Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fujian Medical University, Fuzhou 350001, P.R. China.
Mao-Lin
ML
Yan
Department of Hepatobiliary Surgery, Union Hospital, Fujian Medical University, Fuzhou 350001, PR China.
Yan-Ling
YL
Chen
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.
Cheng-Hong
CH
Peng
Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fujian Medical University, Fuzhou 350001, P.R. China. Electronic address: yifeng0887@126.com.
Yi-Feng
YF
Tian
Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fujian Medical University, Fuzhou 350001, P.R. China. Electronic address: wangyd358@163.com.
Yao-Dong
YD
Wang
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D050687:E2F1 Transcription Factor / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D051381:Rats; D015398:Signal Transduction / Q000235:genetics*
C561518:CDKN2B antisense RNA, human; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D062085:RNA, Long Noncoding; D064007:Ataxia Telangiectasia Mutated Proteins
Epithelial-mesenchymal transition and rat model; Long non-coding RNA ANRIL; Pancreatic cancer; the ATM-E2F1 signaling pathway