TY  - JOUR
AU  - Mudduluru, Giridhar
AU  - Abba, Mohammed Lawan
AU  - Batliner, Jasmin
AU  - Patil, Nitin Shaligram
AU  - Scharp, Maike
AU  - Lunavat, Taral R
AU  - Leupold, Jörg Hendrik
AU  - Oleksiuk, Olga
AU  - Juraeva, Dilafruz
AU  - Thiele, Wilko
AU  - Rothley, Melanie
AU  - Benner, Axel
AU  - Ben-Neriah, Yinon
AU  - Sleeman, Jonathan
AU  - Allgayer, Heike
TI  - A Systematic Approach to Defining the microRNA Landscape in Metastasis.
JO  - Cancer research
VL  - 75
IS  - 15
SN  - 1538-7445
CY  - Philadelphia, Pa.
PB  - AACR
M1  - DKFZ-2017-03203
SP  - 3010 - 3019
PY  - 2015
AB  - 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 N-cadherin 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.
KW  - Antigens, CD (NLM Chemicals)
KW  - CDH2 protein, human (NLM Chemicals)
KW  - Cadherins (NLM Chemicals)
KW  - Cell Cycle Proteins (NLM Chemicals)
KW  - FOXN3 protein, human (NLM Chemicals)
KW  - Homeodomain Proteins (NLM Chemicals)
KW  - MIRN135 microRNA, human (NLM Chemicals)
KW  - MIRN210 microRNA, human (NLM Chemicals)
KW  - MIRN218 microRNA, human (NLM Chemicals)
KW  - MicroRNAs (NLM Chemicals)
KW  - Nuclear Proteins (NLM Chemicals)
KW  - Repressor Proteins (NLM Chemicals)
KW  - ZEB2 protein, human (NLM Chemicals)
KW  - Histone-Lysine N-Methyltransferase (NLM Chemicals)
KW  - Set2 protein, human (NLM Chemicals)
KW  - Ubiquitin-Protein Ligases (NLM Chemicals)
KW  - seven in absentia proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26069251
DO  - DOI:10.1158/0008-5472.CAN-15-0997
UR  - https://inrepo02.dkfz.de/record/127177
ER  -