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NOVA1 acts as an oncogenic RNA-binding protein to regulate cholesterol homeostasis in human glioblastoma cells.
Saito, Yuhki; Yang, Yanhong; Saito, Misa; Park, Christopher Y; Funato, Kosuke; Tabar, Viviane; Darnell, Robert B.
Afiliación
  • Saito Y; HHMI, The Rockefeller University, New York, NY 10065.
  • Yang Y; Laboratory of Molecular Neuro-oncology, The Rockefeller University, New York, NY 10065.
  • Saito M; Department of Neurosurgery, Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
  • Park CY; Cancer Biology and Genetics, Sloan Kettering Institute, New York, NY 10065.
  • Funato K; HHMI, The Rockefeller University, New York, NY 10065.
  • Tabar V; Laboratory of Molecular Neuro-oncology, The Rockefeller University, New York, NY 10065.
  • Darnell RB; HHMI, The Rockefeller University, New York, NY 10065.
Proc Natl Acad Sci U S A ; 121(10): e2314695121, 2024 Mar 05.
Article en En | MEDLINE | ID: mdl-38416679
ABSTRACT
NOVA1 is a neuronal RNA-binding protein identified as the target antigen of a rare autoimmune disorder associated with cancer and neurological symptoms, termed paraneoplastic opsoclonus-myoclonus ataxia. Despite the strong association between NOVA1 and cancer, it has been unclear how NOVA1 function might contribute to cancer biology. In this study, we find that NOVA1 acts as an oncogenic factor in a GBM (glioblastoma multiforme) cell line established from a patient. Interestingly, NOVA1 and Argonaute (AGO) CLIP identified common 3' untranslated region (UTR) targets, which were down-regulated in NOVA1 knockdown GBM cells, indicating a transcriptome-wide intersection of NOVA1 and AGO-microRNA (miRNA) targets regulation. NOVA1 binding to 3'UTR targets stabilized transcripts including those encoding cholesterol homeostasis related proteins. Selective inhibition of NOVA1-RNA interactions with antisense oligonucleotides disrupted GBM cancer cell fitness. The precision of our GBM CLIP studies point to both mechanism and precise RNA sequence sites to selectively inhibit oncogenic NOVA1-RNA interactions. Taken together, we find that NOVA1 is commonly overexpressed in GBM, where it can antagonize AGO2-miRNA actions and consequently up-regulates cholesterol synthesis, promoting cell viability.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glioblastoma / MicroARNs Límite: Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glioblastoma / MicroARNs Límite: Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos