{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:57:47Z","timestamp":1791565067857,"version":"4.3.4"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"41","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82230092"],"award-info":[{"award-number":["82230092"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82025003"],"award-info":[{"award-number":["82025003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82430011"],"award-info":[{"award-number":["82430011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"MOE | Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2042022dx0003"],"award-info":[{"award-number":["2042022dx0003"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82503225"],"award-info":[{"award-number":["82503225"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"MOST | National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2025YFA1309000"],"award-info":[{"award-number":["2025YFA1309000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,10,13]]},"abstract":"<jats:p>\n                    Concurrent chromosomal 17q-gain and\n                    <jats:italic toggle=\"yes\">MYCN<\/jats:italic>\n                    amplification define a subset of neuroblastoma associated with particularly adverse clinical outcomes. However, how these genetic alterations synergize to promote tumor progression and whether their cooperation confers therapeutic vulnerabilities remain elusive. We herein performed a CRISPR-based functional screen targeting 17q-gain genes and identified the RNA m\n                    <jats:sup>6<\/jats:sup>\n                    A reader IGF2BP1 as a critical MYCN collaborator to promote aggressive neuroblastomas via activation of phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), a key enzyme involved in de novo purine biosynthesis. Rewiring of PAICS-mediated nucleotide metabolism enabled tumor cells to sustain necessary purine pools for productive transcription of replicative stress-responsive genes, including\n                    <jats:italic toggle=\"yes\">CHK1<\/jats:italic>\n                    , to cope with the exacerbated replication stress. Pharmacological inhibition of CHK1 elicited a robust immune reprogramming, leading to activation of cGAS\u2013STING signaling, upregulation of Major Histocompatibility Complex class I expression, and synergistic tumor suppression with immune checkpoint blockade. Altogether, we identify an IGF2BP1\/MYCN\u2013PAICS\u2013CHK1 axis that drives aggressive neuroblastoma phenotypes and constitutes an actionable vulnerability for therapeutic intervention.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2524540123","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:31:21Z","timestamp":1791563481000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["IGF2BP1 in 17q-gain cooperates with MYCN to regulate purine biosynthesis and immunotherapy efficacy in neuroblastoma"],"prefix":"10.1073","volume":"123","author":[{"given":"Jiaxu","family":"Liu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Urology, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University","place":["Wuhan, China"]},{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Metabolism and Regulation in Complex Organisms, Taikang Center for Life and Medical Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhe","family":"Fang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Metabolism and Regulation in Complex Organisms, Taikang Center for Life and Medical Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Fan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0220qvk04","id-type":"ROR","asserted-by":"publisher"}],"name":"Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Department of Hematology and Oncology, Biomedical Data Science Center, Pediatric Translational Medicine Institute, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3485-9046","authenticated-orcid":false,"given":"Honghong","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Metabolism and Regulation in Complex Organisms, Taikang Center for Life and Medical Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Huang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Urology, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Urology, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihui","family":"Yu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Urology, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhinang","family":"Yin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Metabolism and Regulation in Complex Organisms, Taikang Center for Life and Medical Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyue","family":"Zhao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Urology, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingping","family":"Zeng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Urology, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5854-1692","authenticated-orcid":false,"given":"Ganggang","family":"Song","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, College of Life Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0220qvk04","id-type":"ROR","asserted-by":"publisher"}],"name":"Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Department of Hematology and Oncology, Biomedical Data Science Center, Pediatric Translational Medicine Institute, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8487-6007","authenticated-orcid":false,"given":"Jinfang","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Metabolism and Regulation in Complex Organisms, Taikang Center for Life and Medical Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Yuan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Metabolism and Regulation in Complex Organisms, Taikang Center for Life and Medical Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiwei","family":"Liang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Metabolism and Regulation in Complex Organisms, Taikang Center for Life and Medical Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6796-9500","authenticated-orcid":false,"given":"Baishan","family":"Jiang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Urology, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1362-6048","authenticated-orcid":false,"given":"Hudan","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Metabolism and Regulation in Complex Organisms, Taikang Center for Life and Medical Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7892-2860","authenticated-orcid":false,"given":"Guoliang","family":"Qing","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Urology, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University","place":["Wuhan, China"]},{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Metabolism and Regulation in Complex Organisms, Taikang Center for Life and Medical Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.78"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0804577"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-022-00643-z"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16020338"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199906243402504"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-007798"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30023-1"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30693-X"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003735"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0554-4"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.09.021"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.09.027"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.11.2985"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00774-x"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0045-z"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.122070"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0044-9"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.05.011"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-3631"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST20220729"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47215-6"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-1020"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1347404"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01899-4"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2022.09.003"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44319-024-00354-9"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01792-0"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2014.269"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.55.9880"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.10.029"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-22-1029"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adf0005"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abn1382"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-0491"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2210859"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.12-11-04460.1992"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.09.027"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe3516"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku365"},{"key":"e_1_3_4_40_2","unstructured":"J. Liu CRISPR-Cas9 screen identify IGF2BP1 as a top essential MYCN-synergizing candidate in the 17q-gain region. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE333426. Deposited 26 May 2026."},{"key":"e_1_3_4_41_2","unstructured":"J. Liu RIP-seq analysis in primary neuroblastoma tumor cells. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE333429. Deposited 26 May 2026."},{"key":"e_1_3_4_42_2","unstructured":"J. Liu RNA-seq analysis in primary neuroblastoma tumor cells. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE333425. Deposited 26 May 2026."},{"key":"e_1_3_4_43_2","unstructured":"J. Liu IGF2BP1 in 17q-gain cooperates with MYCN to regulate purine biosynthesis and immunotherapy efficacy in neuroblastoma. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE333427. Deposited 26 May 2026."},{"key":"e_1_3_4_44_2","unstructured":"J. Liu TT-seq analysis in primary neuroblastoma tumor cells. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE333428. Deposited 26 May 2026."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2524540123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:31:27Z","timestamp":1791563487000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2524540123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,9]]},"references-count":44,"journal-issue":{"issue":"41","published-print":{"date-parts":[[2026,10,13]]}},"alternative-id":["10.1073\/pnas.2524540123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2524540123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,9]]},"assertion":[{"value":"2025-09-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2524540123"}}