A systematic approach to defining the microRNA landscape in metastasis

• Verfasst von: Mudduluru, Giridhar [VerfasserIn]
• Verfasst von: Abba, Mohammed L. [VerfasserIn]
• Verfasst von: Patil, Nitin [VerfasserIn]
• Verfasst von: Leupold, Jörg [VerfasserIn]
• Verfasst von: Thiele, Wilko [VerfasserIn]
• Verfasst von: Rothley, Melanie [VerfasserIn]
• Verfasst von: Sleeman, Jonathan P. [VerfasserIn]
• Verfasst von: Allgayer, Heike [VerfasserIn]
• Titel: A systematic approach to defining the microRNA landscape in metastasis
• Verf.angabe: Giridhar Mudduluru, Mohammed Abba, Jasmin Batliner, Nitin Patil, Maike Scharp, Taral R. Lunavat, Jörg Hendrik Leupold, Olga Oleksiuk, Dilafruz Juraeva, Wilko Thiele, Melanie Rothley, Axel Benner, Yinon Ben-Neriah, Jonathan Sleeman, and Heike Allgayer
• E-Jahr: 2015
• Jahr: August 1, 2015
• Umfang: 10 S.
• Fussnoten: Gesehen am 15.03.2018
• Titel Quelle: Enthalten in: Cancer research
• Ort Quelle: Philadelphia, Pa. : AACR, 1916
• Jahr Quelle: 2015
• Band/Heft Quelle: 75(2015), 15, Seite 3010-3019
• ISSN Quelle: 1538-7445
• DOI: doi:10.1158/0008-5472.CAN-15-0997
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1571100490

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.