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

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Hanniford, Douglas ^{[1, 2]} ; Ulloa-Morales, Alejandro ^{[1, 2]} ; Karz, Alcida ^{[1, 2]} ; Berzoti-Coelho, Maria Gabriela ^{[3, 1]} ; Moubarak, Rana S. ^{[1, 2]} ; Sanchez-Sendra, Beatriz ^[4] ; Kloetgen, Andreas ^{[1, 2]} ; Davalos, Veronica ^[5] ; Imig, Jochen ^{[1, 2]} ; Wu, Pamela ^{[6, 7]} ; Vasudevaraja, Varshini ^[8] ; Argibay, Diana ^{[1, 2]} ; Lilja, Karin ^[1] ; Tabaglio, Tommaso ^[9] ; Monteagudo, Carlos ^[10] ; Guccione, Ernesto ^{[11, 9]} ; Tsirigos, Aristotelis ^{[1, 8]} ; Osman, Iman ^{[2, 12, 13]} ; Aifantis, Iannis ^{[1, 2]} ; Hernando, Eva ^{[1, 2]}

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^[1] NYU, Dept Pathol, Langone Med Ctr, 550 1St Ave, New York, NY 10016 - USA

^[2] NYU, Interdisciplinary Melanoma Cooperat Grp, Langone Med Ctr, New York, NY 10016 - USA

^[3] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Sao Paulo - Brazil

^[4] Univ Valencia, Biomed Res Inst INCLIVA, Valencia - Spain

^[5] Josep Carreras Leukaemia Res Inst IJC, Barcelona, Catalonia - Spain

^[6] NYU, Langone Med Ctr, Inst Syst Genet, New York, NY - USA

^[7] Enigma Technol Inc, New York, NY - USA

^[8] NYU, Langone Med Ctr, Appl Bioinformat Labs, New York, NY - USA

^[9] ASTAR, Inst Mol & Cell Biol, Singapore - Singapore

^[10] Univ Valencia, Dept Pathol, Valencia - Spain

^[11] Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 - USA

^[12] NYU, Dept Urol, Langone Med Ctr, New York, NY - USA

^[13] NYU, Dept Med, Langone Med Ctr, 550 1St Ave, New York, NY 10016 - USA

• Tipo de documento: Artigo Científico
• Fonte: CANCER CELL; v. 37, n. 1, p. 55+, JAN 13 2020.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 17/23501-6 - Papel do CDR1as na tumorigênese e progressão do melanoma através da regulação do miR-7
• Beneficiário: Maria Gabriela Berzoti Coelho
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado