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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,3,5]]},"abstract":"<jats:p>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\u2032 untranslated region (UTR) targets, which were down-regulated in NOVA1 knockdown GBM cells, indicating a transcriptome-wide intersection of NOVA1 and AGO\u2013microRNA (miRNA) targets regulation. NOVA1 binding to 3\u2032UTR targets stabilized transcripts including those encoding cholesterol homeostasis related proteins. Selective inhibition of NOVA1\u2013RNA 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\u2013RNA interactions. Taken together, we find that NOVA1 is commonly overexpressed in GBM, where it can antagonize AGO2\u2013miRNA actions and consequently up-regulates cholesterol synthesis, promoting cell viability.<\/jats:p>","DOI":"10.1073\/pnas.2314695121","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T13:01:01Z","timestamp":1709125261000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":8,"title":["NOVA1 acts as an oncogenic RNA-binding protein to regulate cholesterol homeostasis in human glioblastoma cells"],"prefix":"10.1073","volume":"121","author":[{"given":"Yuhki","family":"Saito","sequence":"first","affiliation":[{"name":"HHMI, The Rockefeller University, New York, NY 10065"},{"name":"Laboratory of Molecular Neuro-oncology, The Rockefeller University, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065"},{"name":"Cancer Biology and Genetics, Sloan Kettering Institute, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misa","family":"Saito","sequence":"additional","affiliation":[{"name":"HHMI, The Rockefeller University, New York, NY 10065"},{"name":"Laboratory of Molecular Neuro-oncology, The Rockefeller University, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher Y.","family":"Park","sequence":"additional","affiliation":[{"name":"HHMI, The Rockefeller University, New York, NY 10065"},{"name":"Laboratory of Molecular Neuro-oncology, The Rockefeller University, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Funato","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065"},{"name":"Cancer Biology and Genetics, Sloan Kettering Institute, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviane","family":"Tabar","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065"},{"name":"Cancer Biology and Genetics, Sloan Kettering Institute, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5134-8088","authenticated-orcid":false,"given":"Robert B.","family":"Darnell","sequence":"additional","affiliation":[{"name":"HHMI, The Rockefeller University, New York, NY 10065"},{"name":"Laboratory of Molecular Neuro-oncology, The Rockefeller University, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"key":"e_1_3_5_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90077-5"},{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra023009"},{"key":"e_1_3_5_3_2","volume-title":"Paraneoplastic Syndromes","author":"Darnell R. 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