Long noncoding RNA LINC01186, regulated by TGF-β/SMAD3, inhibits migration and invasion through Epithelial-Mesenchymal-Transition in lung cancer

被引:57
作者
Hao, Yajing [1 ,2 ,3 ]
Yang, Xinling [1 ,2 ,3 ,4 ]
Zhang, Dongdong [1 ,2 ]
Luo, Jianjun [1 ,2 ]
Chen, Runsheng [1 ,2 ]
机构
[1] Chinese Acad Sci, Inst Biophys, Key Lab RNA Biol, Beijing 100101, Peoples R China
[2] Chinese Acad Sci, Inst Biophys, Beijing Key Lab Noncoding RNA, Beijing 100101, Peoples R China
[3] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
[4] Hebei North Univ, Coll Lab Med, Zhangjiakou 075000, Peoples R China
基金
中国国家自然科学基金;
关键词
Lung cancer; TGF-beta; Long noncoding RNA; Epithelial-Mesenchymal-Transition; SMAD3; DISEASE-FREE SURVIVAL; GENE SET ENRICHMENT; TGF-BETA; BREAST-CANCER; ABERRANT EXPRESSION; COLORECTAL-CANCER; HUMAN GENOME; METASTASIS; SMAD3; CELLS;
D O I
10.1016/j.gene.2017.01.023
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Accumulating evidence suggests that long noncoding RNAs (IncRNAs) are crucial regulators of the Epithelial-Mesenchymal-Transition (EMT). TGF-beta signaling is a major inducer of EMT and can facilitate lung cancer metastasis. However, the role of lncRNAs in this process remains largely unknown. Here, we have identified 291 IncRNAs which were differentially expressed in lung cancer tissues compared with adjacent normal tissues. Of these, the gene body or vicinity of 19 transcripts were also bound by SMAD3. The expression of LINC01186 was significantly decreased in A549 cells treated with TGF-beta. Furthermore, LINC01186 was stably down-regulated in lung cancer tissues compared with normal tissues in TCGA data sets and another published lung cancer data sets. The bioinformatics analysis suggested that LINC01186 was associated with TGF-beta and might participate in EMT process. Moreover, knocking-down LINC01186 promoted cell migration and invasion, whereas, LINC01186 overexpression prevented cell metastasis. Importantly, LINC01186 expression was regulated by SMAD3. And LINC01186 affected several EMT markers expression. These findings suggest that LINC01186, a mediator of TGF-beta signaling, can play a significant role in the regulation of EMT and lung cancer cell migration and invasion. (C) 2017 Elsevier B.V. All rights reserved.
引用
收藏
页码:1 / 12
页数:12
相关论文
共 55 条
  • [1] Ahmed NU, 2001, PIGM CELL RES, V14, P140
  • [2] [Anonymous], PLOS ONE, V10
  • [3] Tumour progression and metastasis
    Arvelo, Francisco
    Sojo, Felipe
    Cotte, Carlos
    [J]. ECANCERMEDICALSCIENCE, 2016, 10
  • [4] Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response
    Ashcroft, GS
    Yang, X
    Glick, AB
    Weinstein, M
    Letterio, JJ
    Mizel, DE
    Anzano, M
    Greenwell-Wild, T
    Wahl, SM
    Deng, CX
    Roberts, AB
    [J]. NATURE CELL BIOLOGY, 1999, 1 (05) : 260 - 266
  • [5] Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
    Birney, Ewan
    Stamatoyannopoulos, John A.
    Dutta, Anindya
    Guigo, Roderic
    Gingeras, Thomas R.
    Margulies, Elliott H.
    Weng, Zhiping
    Snyder, Michael
    Dermitzakis, Emmanouil T.
    Stamatoyannopoulos, John A.
    Thurman, Robert E.
    Kuehn, Michael S.
    Taylor, Christopher M.
    Neph, Shane
    Koch, Christoph M.
    Asthana, Saurabh
    Malhotra, Ankit
    Adzhubei, Ivan
    Greenbaum, Jason A.
    Andrews, Robert M.
    Flicek, Paul
    Boyle, Patrick J.
    Cao, Hua
    Carter, Nigel P.
    Clelland, Gayle K.
    Davis, Sean
    Day, Nathan
    Dhami, Pawandeep
    Dillon, Shane C.
    Dorschner, Michael O.
    Fiegler, Heike
    Giresi, Paul G.
    Goldy, Jeff
    Hawrylycz, Michael
    Haydock, Andrew
    Humbert, Richard
    James, Keith D.
    Johnson, Brett E.
    Johnson, Ericka M.
    Frum, Tristan T.
    Rosenzweig, Elizabeth R.
    Karnani, Neerja
    Lee, Kirsten
    Lefebvre, Gregory C.
    Navas, Patrick A.
    Neri, Fidencio
    Parker, Stephen C. J.
    Sabo, Peter J.
    Sandstrom, Richard
    Shafer, Anthony
    [J]. NATURE, 2007, 447 (7146) : 799 - 816
  • [6] Dependency of Colorectal Cancer on a TGF-β-Driven Program in Stromal Cells for Metastasis Initiation
    Calon, Alexandre
    Espinet, Elisa
    Palomo-Ponce, Sergio
    Tauriello, Daniele V. F.
    Iglesias, Mar
    Virtudes Cespedes, Maria
    Sevillano, Marta
    Nadal, Cristina
    Jung, Peter
    Zhang, Xiang H. -F.
    Byrom, Daniel
    Riera, Antoni
    Rossell, David
    Mangues, Ramon
    Massague, Joan
    Sancho, Elena
    Batlle, Eduard
    [J]. CANCER CELL, 2012, 22 (05) : 571 - 584
  • [7] ANRIL inhibits p15INK4b through the TGFβ1 signaling pathway in human esophageal squamous cell carcinoma
    Chen, Deyu
    Zhang, Zhaoyue
    Mao, Chaoming
    Zhou, Yuepeng
    Yu, Lichao
    Yin, Yue
    Wu, Shi
    Mou, Xiao
    Zhu, Yan
    [J]. CELLULAR IMMUNOLOGY, 2014, 289 (1-2) : 91 - 96
  • [8] Direct binding of Smad3 and Smad4 to critical TGFβ-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene
    Dennler, S
    Itoh, S
    Vivien, D
    ten Dijke, P
    Huet, S
    Gauthier, JM
    [J]. EMBO JOURNAL, 1998, 17 (11) : 3091 - 3100
  • [9] The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression
    Derrien, Thomas
    Johnson, Rory
    Bussotti, Giovanni
    Tanzer, Andrea
    Djebali, Sarah
    Tilgner, Hagen
    Guernec, Gregory
    Martin, David
    Merkel, Angelika
    Knowles, David G.
    Lagarde, Julien
    Veeravalli, Lavanya
    Ruan, Xiaoan
    Ruan, Yijun
    Lassmann, Timo
    Carninci, Piero
    Brown, James B.
    Lipovich, Leonard
    Gonzalez, Jose M.
    Thomas, Mark
    Davis, Carrie A.
    Shiekhattar, Ramin
    Gingeras, Thomas R.
    Hubbard, Tim J.
    Notredame, Cedric
    Harrow, Jennifer
    Guigo, Roderic
    [J]. GENOME RESEARCH, 2012, 22 (09) : 1775 - 1789
  • [10] GENCODE: The reference human genome annotation for The ENCODE Project
    Harrow, Jennifer
    Frankish, Adam
    Gonzalez, Jose M.
    Tapanari, Electra
    Diekhans, Mark
    Kokocinski, Felix
    Aken, Bronwen L.
    Barrell, Daniel
    Zadissa, Amonida
    Searle, Stephen
    Barnes, If
    Bignell, Alexandra
    Boychenko, Veronika
    Hunt, Toby
    Kay, Mike
    Mukherjee, Gaurab
    Rajan, Jeena
    Despacio-Reyes, Gloria
    Saunders, Gary
    Steward, Charles
    Harte, Rachel
    Lin, Michael
    Howald, Cedric
    Tanzer, Andrea
    Derrien, Thomas
    Chrast, Jacqueline
    Walters, Nathalie
    Balasubramanian, Suganthi
    Pei, Baikang
    Tress, Michael
    Manuel Rodriguez, Jose
    Ezkurdia, Iakes
    van Baren, Jeltje
    Brent, Michael
    Haussler, David
    Kellis, Manolis
    Valencia, Alfonso
    Reymond, Alexandre
    Gerstein, Mark
    Guigo, Roderic
    Hubbard, Tim J.
    [J]. GENOME RESEARCH, 2012, 22 (09) : 1760 - 1774