A Systematic Approach to Defining the microRNA Landscape in Metastasis

被引：55

作者：

Mudduluru, Giridhar ^{[1
,2
]}

Abba, Mohammed ^{[1
,2
,3
]}

Batliner, Jasmin ^{[1
,2
]}

Patil, Nitin ^{[1
,2
,3
]}

Scharp, Maike ^{[1
,2
]}

Lunavat, Taral R. ^{[1
,2
]}

Leupold, Joerg Hendrik ^{[1
,2
,3
]}

Oleksiuk, Olga ^{[1
,2
]}

Juraeva, Dilafruz ^{[4
]}

Thiele, Wilko ^{[3
,5
]}

Rothley, Melanie ^{[3
,5
]}

Benner, Axel ^{[6
]}

Ben-Neriah, Yinon ^{[7
,8
]}

Sleeman, Jonathan ^{[3
,5
]}

Allgayer, Heike ^{[1
,3
]}

机构：

[1] Heidelberg Univ, Med Fac Mannheim, Dept Expt Surg, D-68167 Mannheim, Germany

[2] German Canc Res Ctr, Mol Oncol Solid Tumors Unit, Mannheim, Germany

[3] Ctr Biomed & Med Technol Mannheim, Mannheim, Germany

[4] German Canc Res Ctr, Dept Theoret Bioinformat, Heidelberg, Germany

[5] Karlsruhe Inst Technol, Inst Toxicol & Genet, D-76021 Karlsruhe, Germany

[6] German Canc Res Ctr, Dept Biostat, Heidelberg, Germany

[7] Hebrew Univ Jerusalem, Hadassah Med Sch Jerusalem, Lautenberg Ctr Immunol, Jerusalem, Israel

[8] Hebrew Univ Jerusalem, Hadassah Med Sch Jerusalem, Canc Res Inst Med Res Israel Canada, Jerusalem, Israel

来源：

CANCER RESEARCH | 2015年 / 75卷 / 15期

关键词：

GENE-EXPRESSION; TUMOR; CANCER; CELLS; INVASION; CADHERIN; HYPOXIA; PATHWAY; PROTEIN; SETD2;

D O I：

10.1158/0008-5472.CAN-15-0997

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The microRNA (miRNA) landscape changes during the progression of cancer. We defined a metastasis-associated miRNA landscape using a systematic approach. We profiled and validated miRNA and mRNA expression in a unique series of human colorectal metastasis tissues together with their matched primary tumors and corresponding normal tissues. We identified an exclusive miRNA signature that is differentially expressed in metastases. Three of these miRNAs were identified as key drivers of an EMT-regulating network acting though a number of novel targets. These targets include SIAH1, SETD2, ZEB2, and especially FOXN3, which we demonstrated for the first time as a direct transcriptional suppressor of N-cadherin. The modulation of Ncadherin expression had significant impact on migration, invasion, and metastasis in two different in vivo models. The significant deregulation of the miRNAs defining the network was confirmed in an independent patient set as well as in a database of diverse malignancies derived from more than 6,000 patients. Our data define a novel metastasis-orchestrating network based on systematic hypothesis generation from metastasis tissues. (C) 2015 AACR.

引用

页码：3010 / 3019

页数：10

共 37 条

[1] miR-135b Coordinates Progression of ErbB2-Driven Mammary Carcinomas through Suppression of MIDI. and MTCH2 [J].

Arigoni, Maddalena ;

Barutello, Giuseppina ;

Riccardo, Federica ;

Ercole, Elisabetta ;

Cantarella, Daniela ;

Orso, Francesca ;

Conti, Laura ;

Lanzardo, Stefania ;

Taverna, Daniela ;

Merighi, Irene ;

Calogero, Raffaele A. ;

Cavallo, Federica ;

Quaglino, Elena .

AMERICAN JOURNAL OF PATHOLOGY, 2013, 182 (06) :2058-2070

[2] Cadherins and catenins: Role in signal transduction and tumor progression [J].

Behrens, J .

CANCER AND METASTASIS REVIEWS, 1999, 18 (01) :15-30

[3] The ZEB1/miR-200 feedback loop controls Notch signalling in cancer cells [J].

Brabletz, Simone ;

Bajdak, Karolina ;

Meidhof, Simone ;

Burk, Ulrike ;

Niedermann, Gabriele ;

Firat, Elke ;

Wellner, Ulrich ;

Dimmler, Arno ;

Faller, Gerhard ;

Schubert, Joerg ;

Brabletz, Thomas .

EMBO JOURNAL, 2011, 30 (04) :770-782

[4] hsa-miR-210 is induced by hypoxia and is an independent prognostic factor in breast cancer [J].

Camps, Carme ;

Buffa, Francesca M. ;

Colella, Stefano ;

Moore, John ;

Sotiriou, Christos ;

Sheldon, Helen ;

Harris, Adrian L. ;

Gleadle, Jonathan M. ;

Ragoussis, Jiannis .

CLINICAL CANCER RESEARCH, 2008, 14 (05) :1340-1348

[5] Enhanced Expression of EHMT2 Is Involved in the Proliferation of Cancer Cells through Negative Regulation of SIAH1 [J].

Cho, Hyun-Soo ;

Kelly, John D. ;

Hayami, Shinya ;

Toyokawa, Gouji ;

Takawa, Masahi ;

Yoshimatsu, Masanori ;

Tsunoda, Tatsuhiko ;

Field, Helen I. ;

Neal, David E. ;

Ponder, Bruce A. J. ;

Nakamura, Yusuke ;

Hamamoto, Ryuji .

NEOPLASIA, 2011, 13 (08) :676-U33

[6] The chick embryo chorioallantoic membrane as a model to study tumor metastasis [J].

Cimpean, Anca Maria ;

Ribatti, Domenico ;

Raica, Marius .

ANGIOGENESIS, 2008, 11 (04) :311-319

[7] The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion [J].

Comijn, J ;

Berx, G ;

Vermassen, P ;

Verschueren, K ;

van Grunsven, L ;

Bruyneel, E ;

Mareel, M ;

Huylebroeck, D ;

van Roy, F .

MOLECULAR CELL, 2001, 7 (06) :1267-1278

[8] Histone Methyltransferase Gene SETD2 Is a Novel Tumor Suppressor Gene in Clear Cell Renal Cell Carcinoma [J].

Duns, Gerben ;

van den Berg, Eva ;

van Duivenbode, Inge ;

Osinga, Jan ;

Hollema, Harry ;

Hofstra, Robert M. W. ;

Kok, Klaas .

CANCER RESEARCH, 2010, 70 (11) :4287-4291

[9] The mir-200 family and mir-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1 [J].

Gregory, Philip A. ;

Bert, Andrew G. ;

Paterson, Emily L. ;

Barry, Simon C. ;

Tsykin, Anna ;

Farshid, Gelareh ;

Vadas, Mathew A. ;

Khew-Goodall, Yeesim ;

Goodall, Gregory J. .

NATURE CELL BIOLOGY, 2008, 10 (05) :593-601

[10] A microRNA component of the p53 tumour suppressor network [J].

He, Lin ;

He, Xingyue ;

Lim, Lee P. ;

De Stanchina, Elisa ;

Xuan, Zhenyu ;

Liang, Yu ;

Xue, Wen ;

Zender, Lars ;

Magnus, Jill ;

Ridzon, Dana ;

Jackson, Aimee L. ;

Linsley, Peter S. ;

Chen, Caifu ;

Lowe, Scott W. ;

Cleary, Michele A. ;

Hannon, Gregory J. .

NATURE, 2007, 447 (7148) :1130-U16

← 1 2 3 4 →