{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:43:25Z","timestamp":1791895405924,"version":"4.3.4"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:00:00Z","timestamp":1690156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 NS108396"],"award-info":[{"award-number":["R01 NS108396"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["CA224867"],"award-info":[{"award-number":["CA224867"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["CA221282"],"award-info":[{"award-number":["CA221282"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Medulloblastoma is the most common pediatric brain malignancy. Patients with the Group 3 subtype of medulloblastoma (MB) often exhibit MYC amplification and\/or overexpression and have the poorest prognosis. While Group 3 MB is known to be highly dependent on MYC, direct targeting of MYC remains elusive.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Patient gene expression data were used to identify highly expressed EYA2 in Group 3 MB samples, assess the correlation between EYA2 and MYC, and examine patient survival. Genetic and pharmacological studies were performed on EYA2 in Group 3 derived MB cell models to assess MYC regulation and viability in vitro and in vivo.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>EYA2 is more highly expressed in Group 3 MB than other MB subgroups and is essential for Group 3 MB growth in vitro and in vivo. EYA2 regulates MYC expression and protein stability in Group 3 MB, resulting in global alterations of MYC transcription. Inhibition of EYA2 tyrosine phosphatase activity, using a novel small molecule inhibitor (NCGC00249987, or 9987), significantly decreases Group 3 MB MYC expression in both flank and intracranial growth in vivo. Human MB RNA-seq data show that EYA2 and MYC are significantly positively correlated, high EYA2 expression is significantly associated with a MYC transcriptional signature, and patients with high EYA2 and MYC expression have worse prognoses than those that do not express both genes at high levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our data demonstrate that EYA2 is a critical regulator of MYC in Group 3 MB and suggest a novel therapeutic avenue to target this highly lethal disease.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/neuonc\/noad128","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T22:33:38Z","timestamp":1689978818000},"page":"2287-2301","source":"Crossref","is-referenced-by-count":15,"title":["EYA2 tyrosine phosphatase inhibition reduces MYC and prevents medulloblastoma progression"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1881-390X","authenticated-orcid":false,"given":"Arthur R","family":"Wolin","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Colorado Anschutz Medical Campus (AMC) , Aurora, Colorado , USA"},{"name":"Molecular Biology Graduate Program, University of Colorado AMC , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie Y","family":"Vincent","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Colorado Anschutz Medical Campus (AMC) , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Hotz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Colorado Anschutz Medical Campus (AMC) , Aurora, Colorado , 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