Epigenetic Silencing of CDR1as Drives IGF2BP3-Mediated Melanoma Invasion and Metastasis

Publication date: 13 January 2020Source: Cancer Cell, Volume 37, Issue 1Author(s): Douglas Hanniford, Alejandro Ulloa-Morales, Alcida Karz, Maria Gabriela Berzoti-Coelho, Rana S. Moubarak, Beatriz Sánchez-Sendra, Andreas Kloetgen, Veronica Davalos, Jochen Imig, Pamela Wu, Varshini Vasudevaraja, Diana Argibay, Karin Lilja, Tommaso Tabaglio, Carlos Monteagudo, Ernesto Guccione, Aristotelis Tsirigos, Iman Osman, Iannis Aifantis, Eva HernandoSummaryMetastasis is the primary cause of death of cancer patients. Dissecting mechanisms governing metastatic spread may uncover important tumor biology and/or yield promising therapeutic insights. Here, we investigated the role of circular RNAs (circRNA) in metastasis, using melanoma as a model aggressive tumor. We identified silencing of cerebellar degeneration-related 1 antisense (CDR1as), a regulator of miR-7, as a hallmark of melanoma progression. CDR1as depletion results from epigenetic silencing of LINC00632, its originating long non-coding RNA (lncRNA) and promotes invasion in vitro and metastasis in vivo through a miR-7-independent, IGF2BP3-mediated mechanism. Moreover, CDR1as levels reflect cellular states associated with distinct therapeutic responses. Our study reveals functional, prognostic, and predictive roles for CDR1as and expose circRNAs as key players in metastasis.Graphical Abstract
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research