Upregulated MALAT-1 contributes to bladder cancer cell migration by inducing epithelial-to-mesenchymal transition

被引：320

作者：

Ying, Liang ^{[1
]}

Chen, Qi ^{[1
]}

Wang, Yawei ^{[1
]}

Zhou, Zhihua ^{[1
]}

Huang, Yiran ^{[1
]}

Qiu, Feng ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Urol, Shanghai 200127, Peoples R China

来源：

MOLECULAR BIOSYSTEMS | 2012年 / 8卷 / 09期

关键词：

LONG NONCODING RNA; E-CADHERIN EXPRESSION; BREAST-CANCER; HUMAN CARCINOMAS; PROLIFERATION; METASTASIS; HYPOXIA; CATENIN; BINDING; GENOME;

D O I：

10.1039/c2mb25070e

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Recent studies reveal that long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology, and lncRNA MALAT-1 expression is upregulated in some tumors. However, the contributions of MALAT-1 to bladder cancer metastasis remain largely unknown. In the present study we evaluated MALAT-1 expression in bladder cancer tissues by real-time PCR, and defined its biological functions. We verified that MALAT-1 levels were upregulated in bladder cancer tissues compared with adjacent normal tissues, and MALAT-1 expression was remarkably increased in primary tumors that subsequently metastasized, when compared to those primary tumors that did not metastasize. SiRNA-mediated MALAT-1 silencing impaired in vitro bladder cancer cell migration. Downregulation of MALAT-1 resulted in a decrease of the epithelial-mesenchymal transition (EMT)-associated ZEB1, ZEB2 and Slug levels, and an increase of E-cadherin levels. We further demonstrated that MALAT-1 promoted EMT by activating Wnt signaling in vitro. These data suggest an important role for MALAT-1 in regulating metastasis of bladder cancer and the potential application of MALAT-1 in bladder cancer therapy.

引用

页码：2289 / 2294

页数：6

共 30 条

[1] The c-Myc oncogene directly induces the H19 noncoding RNA by allele-specific binding to potentiate tumorigenesis [J].

Barsyte-Lovejoy, Dalia ;

Lau, Suzanne K. ;

Boutros, Paul C. ;

Khosravi, Fereshteh ;

Jurisica, Igor ;

Andrulis, Irene L. ;

Tsao, Ming S. ;

Penn, Linda Z. .

CANCER RESEARCH, 2006, 66 (10) :5330-5337

[2] H19 mRNA-like noncoding RNA promotes breast cancer cell proliferation through positive control by E2F1 [J].

Berteaux, N ;

Lottin, V ;

Monté, D ;

Pinte, S ;

Quatannens, B ;

Coll, J ;

Hondermarck, H ;

Curgy, JJ ;

Dugimont, T ;

Adriaenssens, E .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (33) :29625-29636

[3] microRNA-203 suppresses bladder cancer development by repressing bcl-w expression [J].

Bo, Juanjie ;

Yang, Guoliang ;

Huo, Kailing ;

Jiang, Haifeng ;

Zhang, Lianhua ;

Liu, Dongming ;

Huang, Yiran .

FEBS JOURNAL, 2011, 278 (05) :786-792

[4] NF-κB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells:: potential involvement of ZEB-1 and ZEB-2 [J].

Chua, H. L. ;

Bhat-Nakshatri, P. ;

Clare, S. E. ;

Morimiya, A. ;

Badve, S. ;

Nakshatri, H. .

ONCOGENE, 2007, 26 (05) :711-724

[5] Interaction and functional collaboration of p300/CBP and bHLH proteins in muscle and B-cell differentiation [J].

Eckner, R ;

Yao, TP ;

Oldread, E ;

Livingston, DM .

GENES & DEVELOPMENT, 1996, 10 (19) :2478-2490

[6] Epithelial mesenchymal transition by c-Fos estrogen receptor activation involves nuclear translocation of β-catenin and upregulation of β-catenin/lymphoid enhancer binding factor-1 transcriptional activity [J].

Eger, A ;

Stockinger, A ;

Schaffhauser, B ;

Beug, H ;

Foisner, R .

JOURNAL OF CELL BIOLOGY, 2000, 148 (01) :173-187

[7] H19 expression in hepatic metastases from a range of human carcinomas [J].

Fellig, Y ;

Ariel, I ;

Ohana, P ;

Schachter, P ;

Sinelnikov, I ;

Birman, T ;

Ayesh, S ;

Schneider, T ;

de Groot, N ;

Czerniak, A ;

Hochberg, A .

JOURNAL OF CLINICAL PATHOLOGY, 2005, 58 (10) :1064-1068

[8] The functional role of long non-coding RNA in human carcinomas [J].

Gibb, Ewan A. ;

Brown, Carolyn J. ;

Lam, Wan L. .

MOLECULAR CANCER, 2011, 10

[9] Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis [J].

Gupta, Rajnish A. ;

Shah, Nilay ;

Wang, Kevin C. ;

Kim, Jeewon ;

Horlings, Hugo M. ;

Wong, David J. ;

Tsai, Miao-Chih ;

Hung, Tiffany ;

Argani, Pedram ;

Rinn, John L. ;

Wang, Yulei ;

Brzoska, Pius ;

Kong, Benjamin ;

Li, Rui ;

West, Robert B. ;

van de Vijver, Marc J. ;

Sukumar, Saraswati ;

Chang, Howard Y. .

NATURE, 2010, 464 (7291) :1071-U148

[10] MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer [J].

Ji, P ;

Diederichs, S ;

Wang, WB ;

Böing, S ;

Metzger, R ;

Schneider, PM ;

Tidow, N ;

Brandt, B ;

Buerger, H ;

Bulk, E ;

Thomas, M ;

Berdel, WE ;

Serve, H ;

Müller-Tidow, C .

ONCOGENE, 2003, 22 (39) :8031-8041

← 1 2 3 →