6533b7d1fe1ef96bd125ce0e

RESEARCH PRODUCT

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

Rana S. MoubarakAndreas KloetgenIannis AifantisPamela WuBeatriz Sánchez-sendraCarlos MonteagudoMaria Gabriela Berzoti-coelhoMaria Gabriela Berzoti-coelhoErnesto GuccioneErnesto GuccioneVeronica DavalosTommaso TabaglioVarshini VasudevarajaAlejandro Ulloa-moralesIman OsmanKarin C. LiljaAristotelis TsirigosEva HernandoDouglas HannifordAlcida KarzDiana ArgibayJochen Imig

subject

0301 basic medicineCancer ResearchRegulatorNerve Tissue ProteinsBiologyAutoantigensArticleMetastasisEpigenesis Genetic03 medical and health sciences0302 clinical medicinemedicineGene silencingHumansEnhancer of Zeste Homolog 2 ProteinNeoplasm InvasivenessRNA AntisenseGene SilencingNeoplasm MetastasisMelanomaMelanomaEZH2RNACancerRNA-Binding ProteinsRNA Circularmedicine.diseasePhospholipid Hydroperoxide Glutathione PeroxidasePrognosisMicroRNAs030104 developmental biologyOncology030220 oncology & carcinogenesisCancer researchbiology.proteinRNA Long NoncodingPRC2

description

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.

yearjournalcountryeditionlanguage
2018-07-29Cancer cell
10.1016/j.ccell.2019.12.007https://pubmed.ncbi.nlm.nih.gov/31935372