{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:52:18Z","timestamp":1782276738803,"version":"3.54.5"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,3,6]],"date-time":"2017-03-06T00:00:00Z","timestamp":1488758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Jiaotong University School of Medicine Doctoral Innovation Foundation","award":["BXJ201634"],"award-info":[{"award-number":["BXJ201634"]}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:p>While treatments for childhood osteosarcoma have improved, the overall survival for this common type of bone cancer has not changed for three decades, and thus, new targets for therapeutic development are needed. To identify tumor\u2010related proteins in osteosarcoma, we used isobaric tags in a relative and absolute quantitation proteomic approach to analyze the differentially expressed proteins between osteosarcoma cells and human osteoblastic cells. Through clinical screening and functional evaluation, CCR4\u2013NOT transcription complex subunit 1 (<jats:styled-content style=\"fixed-case\">CNOT<\/jats:styled-content>1) correlated with the growth of osteosarcoma cells. To date, the mechanisms and regulatory roles of <jats:styled-content style=\"fixed-case\">CNOT<\/jats:styled-content>1 in tumors, including osteosarcoma, remain largely elusive. Here, we present evidence that knockdown of <jats:styled-content style=\"fixed-case\">CNOT<\/jats:styled-content>1 inhibits the growth of osteosarcoma <jats:italic>in\u00a0vitro<\/jats:italic> and <jats:italic>in\u00a0vivo<\/jats:italic>. Mechanistically, we observed that <jats:styled-content style=\"fixed-case\">CNOT<\/jats:styled-content>1 interacted with <jats:styled-content style=\"fixed-case\">LMNA<\/jats:styled-content> (lamin A) and functioned as a positive regulator of this intermediate filament protein. The <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010seq analysis revealed that <jats:styled-content style=\"fixed-case\">CNOT<\/jats:styled-content>1 depletion inhibited the Hedgehog signaling pathway in osteosarcoma cells. A rescue study showed that the decreased growth of osteosarcoma cells and inhibition of the Hedgehog signaling pathway by <jats:styled-content style=\"fixed-case\">CNOT<\/jats:styled-content>1 depletion were reversed by <jats:styled-content style=\"fixed-case\">LMNA<\/jats:styled-content> overexpression, indicating that the activity of <jats:styled-content style=\"fixed-case\">CNOT<\/jats:styled-content>1 was <jats:styled-content style=\"fixed-case\">LMNA<\/jats:styled-content> dependent. Notably, the <jats:styled-content style=\"fixed-case\">CNOT<\/jats:styled-content>1 expression was significantly associated with tumor recurrence, Enneking stage, and poor survival in patients with osteosarcoma. Examination of clinical samples confirmed that <jats:styled-content style=\"fixed-case\">CNOT<\/jats:styled-content>1 expression positively correlated with <jats:styled-content style=\"fixed-case\">LMNA<\/jats:styled-content> protein expression. Taken together, these results suggest that the <jats:styled-content style=\"fixed-case\">CNOT<\/jats:styled-content>1\u2013<jats:styled-content style=\"fixed-case\">LMNA<\/jats:styled-content>\u2013Hedgehog signaling pathway axis exerts an oncogenic role in osteosarcoma progression, which could be a potential target for gene therapy.<\/jats:p>","DOI":"10.1002\/1878-0261.12043","type":"journal-article","created":{"date-parts":[[2017,2,11]],"date-time":"2017-02-11T08:12:48Z","timestamp":1486800768000},"page":"388-404","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["<scp>CNOT<\/scp>1 cooperates with <scp>LMNA<\/scp> to aggravate osteosarcoma tumorigenesis through the Hedgehog signaling pathway"],"prefix":"10.1002","volume":"11","author":[{"given":"Dong\u2010dong","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Orthopedics Shanghai Jiao Tong University Affiliated Sixth People's Hospital China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Renji Hospital Shanghai Jiao Tong University School of Medicine China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi\u2010jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Jiao Tong University Affiliated Sixth People's Hospital China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing\u2010cheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Jiao Tong University Affiliated Sixth People's Hospital China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cun\u2010yi","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Jiao Tong University Affiliated Sixth People's Hospital China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-1468"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2016.04.004"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1586\/14789450.2014.900445"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-195739040-00002"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-13-100"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr900113w"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12258"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-9-5"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-011-1092-4"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2014.05.009"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2013.07.022"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers7020784"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2015.11.014"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergencyto.2010.01.003"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3mb00013c"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr400273z"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2014.03.006"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-9-81"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/17453670810016966"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096593"},{"key":"e_1_2_9_22_1","first-page":"681","article-title":"Hedgehog signalling in medulloblastoma, glioblastoma and neuroblastoma","volume":"19","author":"Shahi MH","year":"2008","journal-title":"Oncol Rep"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01676-12"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2015.04.021"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.2145110"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002988"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601194"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S105787"},{"key":"e_1_2_9_29_1","first-page":"8480","article-title":"LKB1 suppresses proliferation and invasion of prostate cancer through hedgehog signaling pathway","volume":"7","author":"Xu P","year":"2014","journal-title":"Int J Clin Exp Pathol"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2015.11.003"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.13749"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2012.04.002"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365521.2016.1190399"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-10-206"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2219"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1089\/cbr.2014.1661"}],"container-title":["Molecular Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2F1878-0261.12043","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1878-0261.12043","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T08:40:11Z","timestamp":1696236011000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/1878-0261.12043"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,6]]},"references-count":35,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2017,4]]}},"alternative-id":["10.1002\/1878-0261.12043"],"URL":"https:\/\/doi.org\/10.1002\/1878-0261.12043","archive":["Portico"],"relation":{},"ISSN":["1574-7891","1878-0261"],"issn-type":[{"value":"1574-7891","type":"print"},{"value":"1878-0261","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,6]]},"assertion":[{"value":"2016-11-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-02-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-03-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}