A long noncoding RNA activated by TGF-β promotes the invasion-metastasis cascade in hepatocellular carcinoma.
The role of TGF-β-induced epithelial-mesenchymal transition (EMT) in cancer cell dissemination is well established, but the involvement of lncRNAs in TGF-β signaling is still unknown. In this study, we observed that the lncRNA-activated by TGF-β (lncRNA-ATB) was upregulated in hepatocellular carcinoma (HCC) metastases and associated with poor prognosis. lncRNA-ATB upregulated ZEB1 and ZEB2 by competitively binding the miR-200 family and then induced EMT and invasion. In addition, lncRNA-ATB promoted organ colonization of disseminated tumor cells by binding IL-11 mRNA, autocrine induction of IL-11, and triggering STAT3 signaling. Globally, lncRNA-ATB promotes the invasion-metastasis cascade. Thus, these findings suggest that lncRNA-ATB, a mediator of TGF-β signaling, could predispose HCC patients to metastases and may serve as a potential target for antimetastatic therapies.
Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
Ji-hang
JH
Yuan
Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
Fu
F
Yang
Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
Fang
F
Wang
Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
Jin-zhao
JZ
Ma
Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
Ying-jun
YJ
Guo
The Third Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, 200433, China.
Qi-fei
QF
Tao
Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
Feng
F
Liu
Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
Wei
W
Pan
Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
Tian-tian
TT
Wang
Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
Chuan-chuan
CC
Zhou
Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
Shao-bing
SB
Wang
Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
Yu-zhao
YZ
Wang
The Third Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, 200433, China.
Yuan
Y
Yang
The Fifth Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, 200433, China.
Ning
N
Yang
The Third Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, 200433, China.
Wei-ping
WP
Zhou
The Fifth Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, 200433, China.
Guang-shun
GS
Yang
Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China. Electronic address: shsun@vip.sina.com.
Shu-han
SH
Sun
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D017370:Interleukin-11 / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
D018398:Homeodomain Proteins; C508611:IL11 protein, human; D017370:Interleukin-11; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1; C000619854:long non-coding RNA ATB, human