Journal Article

DKFZ-2017-03203

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A Systematic Approach to Defining the microRNA Landscape in Metastasis.

Mudduluru, G. (First author)DKFZ* ; Abba, M. L.DKFZ* ; Batliner, J.DKFZ* ; Patil, N. S.DKFZ* ; Scharp, M.DKFZ* ; Lunavat, T. R.DKFZ* ; Leupold, J. H.DKFZ* ; Oleksiuk, O.DKFZ* ; Juraeva, D.DKFZ* ; Thiele, W. ; Rothley, M. ; Benner, A.DKFZ* ; Ben-Neriah, Y. ; Sleeman, J. ; Allgayer, H. (Last author)DKFZ*

2015
AACR Philadelphia, Pa.

This record in other databases:  

Please use a persistent id in citations: doi:10.1158/0008-5472.CAN-15-0997

Abstract: 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.

Keyword(s): Antigens, CD ; CDH2 protein, human ; Cadherins ; Cell Cycle Proteins ; FOXN3 protein, human ; Homeodomain Proteins ; MIRN135 microRNA, human ; MIRN210 microRNA, human ; MIRN218 microRNA, human ; MicroRNAs ; Nuclear Proteins ; Repressor Proteins ; ZEB2 protein, human ; Histone-Lysine N-Methyltransferase ; Set2 protein, human ; Ubiquitin-Protein Ligases ; seven in absentia proteins

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Contributing Institute(s):

1. DKTK Berlin (L201)
2. KKE Molekulare Onkologie solider Tumoren (G360)
3. Biostatistik (C060)
4. Angewandte Bioinformatik (G200)

Research Program(s):

1. 317 - Translational cancer research (POF3-317) (POF3-317)

Appears in the scientific report 2015

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Database coverage:
; BIOSIS Previews ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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