Epigenetic Silencing of CDR1as Drives IGF2BP3-Mediated Melanoma Invasion and Metastasis
| Autor: | Rana S. Moubarak, Andreas Kloetgen, Iannis Aifantis, Pamela Wu, Beatriz Sánchez-Sendra, Carlos Monteagudo, Maria Gabriela Berzoti-Coelho, Ernesto Guccione, Veronica Davalos, Tommaso Tabaglio, Varshini Vasudevaraja, Alejandro Ulloa-Morales, Iman Osman, Karin C. Lilja, Aristotelis Tsirigos, Eva Hernando, Douglas Hanniford, Alcida Karz, Diana Argibay, Jochen Imig |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Regulator Nerve Tissue Proteins Biology Autoantigens Article Metastasis Epigenesis Genetic 03 medical and health sciences 0302 clinical medicine medicine Gene silencing Humans Enhancer of Zeste Homolog 2 Protein Neoplasm Invasiveness RNA Antisense Gene Silencing Neoplasm Metastasis Melanoma EZH2 RNA Cancer RNA-Binding Proteins RNA Circular medicine.disease Phospholipid Hydroperoxide Glutathione Peroxidase Prognosis MicroRNAs 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research biology.protein RNA Long Noncoding PRC2 |
| Zdroj: | Cancer Cell |
| ISSN: | 1878-3686 |
| Popis: | Summary Metastasis 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. |
| Databáze: | OpenAIRE |
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