LncRNA UCA1 promotes tumor metastasis by inducing miR-203/ZEB2 axis in gastric cancer

被引:74
作者
Gong, Pihai [1 ,2 ]
Qiao, Fengchang [1 ,2 ]
Wu, Huazhang [1 ,2 ]
Cui, He [1 ,2 ]
Li, Yiping [3 ]
Zheng, Ying [1 ,2 ]
Zhou, Menghan [1 ,2 ]
Fan, Hong [1 ]
机构
[1] Southeast Univ, Minist Educ, Key Lab Dev Genes & Human Dis, Dept Med Genet & Dev Biol,Med Sch, Nanjing, Jiangsu, Peoples R China
[2] Southeast Univ, Sch Life Sci, Nanjing, Jiangsu, Peoples R China
[3] Southeast Univ, Med Sch, Dept Pathophysiol, Nanjing, Jiangsu, Peoples R China
来源
CELL DEATH & DISEASE | 2018年 / 9卷
基金
中国国家自然科学基金;
关键词
NONCODING RNA UCA1; CARDIOMYOCYTE APOPTOSIS; CELL-PROLIFERATION; LONG; CARCINOMA; INVASION; EZH2; PROGRESSION; MIGRATION; ZEB2;
D O I
10.1038/s41419-018-1170-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Increasing studies showed that long-noncoding RNAs (lncRNAs) play important roles in the biological processes, including cancer initiation and progression. However, little is known about the exact role and regulation mechanism of lncRNA UCA1 during the progression of gastric cancer (GC). In this study, we found that UCA1 was aberrantly elevated in gastric cancer tissues, and was significantly associated with lymph node metastasis and TNM stage. In vivo and in vitro, enforced UCA1 level promoted cell migration and invasion of GC cell. Depleted UCA1 expression level attenuated the ability of cell migration and invasion in GC. And then, we detected that expression level of ZEB2, a transcription factor related to tumor metastasis, was regulated by UCA1 in GC cells. miR-203 targets and suppresses to ZEB2 expression. Furthermore, we found that UCA1 could directly interact with miR-203 and lead to the release of miR203-targeted transcripts ZEB2. Herein, we revealed the novel mechanism of UCA1 on regulating metastasis-related gene by sponge regulatory axis during GC metastasis. Our findings indicated that UCA1 plays a critical role in metastatic GC by mediating sponge regulatory axis miR-203/ZEB2. To explore function of UCA1-miR-203-ZEB2 axis may provide an informative biomarker of malignancy and a highly selective anti-GC therapeutic target.
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页数:14
相关论文
共 49 条
  • [1] Smooth Muscle Enriched Long Noncoding RNA (SMILR) Regulates Cell Proliferation
    Ballantyne, Margaret D.
    Pinel, Karine
    Dakin, Rachel
    Vesey, Alex T.
    Diver, Louise
    Mackenzie, Ruth
    Garcia, Raquel
    Welsh, Paul
    Sattar, Naveed
    Hamilton, Graham
    Joshi, Nikhil
    Dweck, Marc R.
    Miano, Joseph M.
    McBride, Martin W.
    Newby, David E.
    McDonald, Robert A.
    Baker, Andrew H.
    [J]. CIRCULATION, 2016, 133 (21) : 2050 - 2065
  • [2] Comprehensive molecular characterization of gastric adenocarcinoma
    Bass, Adam J.
    Thorsson, Vesteinn
    Shmulevich, Ilya
    Reynolds, Sheila M.
    Miller, Michael
    Bernard, Brady
    Hinoue, Toshinori
    Laird, Peter W.
    Curtis, Christina
    Shen, Hui
    Weisenberger, Daniel J.
    Schultz, Nikolaus
    Shen, Ronglai
    Weinhold, Nils
    Keiser, David P.
    Bowlby, Reanne
    Sipahimalani, Payal
    Cherniack, Andrew D.
    Getz, Gad
    Liu, Yingchun
    Noble, Michael S.
    Pedamallu, Chandra
    Sougnez, Carrie
    Taylor-Weiner, Amaro
    Akbani, Rehan
    Lee, Ju-Seog
    Liu, Wenbin
    Mills, Gordon B.
    Yang, Da
    Zhang, Wei
    Pantazi, Angeliki
    Parfenov, Michael
    Gulley, Margaret
    Piazuelo, M. Blanca
    Schneider, Barbara G.
    Kim, Jihun
    Boussioutas, Alex
    Sheth, Margi
    Demchok, John A.
    Rabkin, Charles S.
    Willis, Joseph E.
    Ng, Sam
    Garman, Katherine
    Beer, David G.
    Pennathur, Arjun
    Raphael, Benjamin J.
    Wu, Hsin-Ta
    Odze, Robert
    Kim, Hark K.
    Bowen, Jay
    [J]. NATURE, 2014, 513 (7517) : 202 - 209
  • [3] The Snail repressor recruits EZH2 to specific genomic sites through the enrollment of the lncRNA HOTAIR in epithelial-to-mesenchymal transition
    Battistelli, C.
    Cicchini, C.
    Santangelo, L.
    Tramontano, A.
    Grassi, L.
    Gonzalez, F. J.
    de Nonno, V.
    Grassi, G.
    Amicone, L.
    Tripodi, M.
    [J]. ONCOGENE, 2017, 36 (07) : 942 - 955
  • [4] LncRNA-UCA1 enhances cell proliferation and 5-fluorouracil resistance in colorectal cancer by inhibiting miR-204-5p
    Bian, Zehua
    Jin, Liugen
    Zhang, Jiwei
    Yin, Yuan
    Quan, Chao
    Hu, Yaling
    Feng, Yuyang
    Liu, Heyong
    Fei, Bojian
    Mao, Yong
    Zhou, Leyuan
    Qi, Xiaowei
    Huang, Shenlin
    Hua, Dong
    Xing, Chungen
    Huang, Zhaohui
    [J]. SCIENTIFIC REPORTS, 2016, 6
  • [5] Regulation of vimentin by SIP1 in human epithelial breast tumor cells
    Bindels, S.
    Mestdagt, M.
    Vandewalle, C.
    Jacobs, N.
    Volders, L.
    Noel, A.
    van Roy, F.
    Berx, G.
    Foidart, J-M
    Gilles, C.
    [J]. ONCOGENE, 2006, 25 (36) : 4975 - 4985
  • [6] High expression of GPR116 indicates poor survival outcome and promotes tumor progression in colorectal carcinoma
    Yang, Li
    Lin, Xiao-Lu
    Liang, Wei
    Fu, Seng-Wang
    Lin, Wen-Feng
    Tian, Xiao-Qing
    Gao, Yun-Jie
    Chen, Hao-Yan
    Dai, Jun
    Ge, Zhi-Zheng
    [J]. ONCOTARGET, 2017, 8 (29) : 47943 - 47956
  • [7] Long non-coding RNA SNHG20 promotes non-small cell lung cancer cell proliferation and migration by epigenetically silencing of P21 expression
    Chen, Zhenyao
    Chen, Xin
    Chen, Ping
    Yu, Shanxun
    Nie, Fengqi
    Lu, Binbin
    Zhang, Te
    Zhou, Yue
    Chen, Qinnan
    Wei, Chenchen
    Wang, Wei
    Wang, Zhaoxia
    [J]. CELL DEATH & DISEASE, 2017, 8 : e3092 - e3092
  • [8] ZEB2 Promotes the Metastasis of Gastric Cancer and Modulates Epithelial Mesenchymal Transition of Gastric Cancer Cells
    Dai, Ying-Huan
    Tang, Ya-Ping
    Zhu, Hong-Yi
    Lv, Liang
    Chu, Yi
    Zhou, Yu-Qian
    Huo, Ji-Rong
    [J]. DIGESTIVE DISEASES AND SCIENCES, 2012, 57 (05) : 1253 - 1260
  • [9] Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer
    Du, Zhou
    Fei, Teng
    Verhaak, Roel G. W.
    Su, Zhen
    Zhang, Yong
    Brown, Myles
    Chen, Yiwen
    Liu, X. Shirley
    [J]. NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2013, 20 (07) : 908 - +
  • [10] Direct interaction between miR-203 and ZEB2 suppresses epithelial-mesenchymal transition signaling and reduces lung adenocarcinoma chemoresistance
    Duan, Xunhuang
    Fu, Zhaojian
    Gao, Lingyuan
    Zhou, Jin
    Deng, Xiaojie
    Luo, Xiaojun
    Fang, Weiyi
    Luo, Rongcheng
    [J]. ACTA BIOCHIMICA ET BIOPHYSICA SINICA, 2016, 48 (11) : 1042 - 1049