{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:29:16Z","timestamp":1790872156561,"version":"4.1.0"},"reference-count":52,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T00:00:00Z","timestamp":1700611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82002513,82073383"],"award-info":[{"award-number":["82002513,82073383"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the National Key R&D Program of China","award":["2018YFC1313000,2018YFC1313001"],"award-info":[{"award-number":["2018YFC1313000,2018YFC1313001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,22]]},"abstract":"<jats:p>\n                    Neuroblastomas have shed light on the differentiation disorder that is associated with spontaneous regression or differentiation in the same tumor at the same time. Long noncoding RNAs (lncRNAs) actively participate in a broad spectrum of biological processes. However, the detailed molecular mechanisms underlying lncRNA regulation of differentiation in neuroblastomas remain largely unknown. Here, we sequenced clinical samples of ganglioneuroma, ganglioneuroblastoma, and neuroblastoma. We compared transcription profiles of neuroblastoma cells, ganglion cells, and intermediate state cells; verified the profiles in a retinoic acid\u2013induced cell differentiation model and clinical samples; and screened out the lncRNA ADAMTS9 antisense RNA 2 (\n                    <jats:italic>ADAMTS9-AS2<\/jats:italic>\n                    ), which contributed to neuroblastoma differentiation.\n                    <jats:italic>ADAMTS9-AS2<\/jats:italic>\n                    upregulation in neuroblastoma cell lines inhibited proliferation and metastatic potential. Additional mechanistic studies illustrated that the interactions between\n                    <jats:italic>ADAMTS9-AS2<\/jats:italic>\n                    and LIN28B inhibited the association between LIN28B and primary let-7 (\n                    <jats:italic>pri-let-7<\/jats:italic>\n                    ) miRNA, then released\n                    <jats:italic>pri-let-7<\/jats:italic>\n                    into cytoplasm to form mature\n                    <jats:italic>let-7<\/jats:italic>\n                    , resulting in the inhibition of oncogene MYCN activity that subsequently affected cancer stemness and differentiation. Furthermore, we showed that the observed differential expression of\n                    <jats:italic>ADAMTS9-AS2<\/jats:italic>\n                    in neuroblastoma cells was due to N\n                    <jats:sup>6<\/jats:sup>\n                    -methyladenosine methylation. Finally,\n                    <jats:italic>ADAMTS9-AS2<\/jats:italic>\n                    upregulation inhibited proliferation and cancer stem-like capabilities in vivo. Taken together, these results show that\n                    <jats:italic>ADAMTS9-AS2<\/jats:italic>\n                    loss leads to malignant neuroblastoma by increasing metastasis and causing dysfunctional differentiation.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.165703","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T14:00:56Z","timestamp":1700575256000},"source":"Crossref","is-referenced-by-count":12,"title":["N6-methyladenosine\u2013mediated overexpression of long noncoding RNA ADAMTS9-AS2 triggers neuroblastoma differentiation via regulating LIN28B\/let-7\/MYCN signaling"],"prefix":"10.1172","volume":"8","author":[{"given":"Yun","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, and"},{"name":"Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The Second Hospital of Tianjin Medical University, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, and"},{"name":"Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobao","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, and"},{"name":"Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, and"},{"name":"Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanna","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, and"},{"name":"Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanglin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, and"},{"name":"Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, and"},{"name":"Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, and"},{"name":"Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Tianjin Medical University Cancer 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