{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:31:03Z","timestamp":1790692263256,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,10,5]],"date-time":"2024-10-05T00:00:00Z","timestamp":1728086400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172839"],"award-info":[{"award-number":["82172839"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82374229"],"award-info":[{"award-number":["82374229"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82203120"],"award-info":[{"award-number":["82203120"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Radiotherapy is a primary therapeutic modality for esophageal squamous cell carcinoma (ESCC), but its effectiveness is still restricted due to the resistance of cancer cells to radiation. Long non\u2010coding RNAs (lncRNAs) and N<jats:sup>6<\/jats:sup>\u2010methyladenosine (m6A) have been shown to play significant roles in tumour radioresistance. However, the precise manifestation and role of m6A\u2010modified lncRNAs in ESCC radioresistance remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Bioinformatics analysis was conducted to identify m6A\u2010modified lncRNAs implicated in the radioresistance of ESCC. A series of functional experiments were performed to investigate the function of LNCAROD in ESCC. Methylated RNA immunoprecipitation, chromatin isolation by RNA purification\u2010mass spectrometry, RNA immunoprecipitation, and co\u2010immunoprecipitation experiments were performed to explore the mechanism of m6A\u2010mediated upregulation of LNCAROD expression and the downstream mechanism enhancing the radioresistance of ESCC. The efficacy of LNCAROD in vivo was assessed using murine xenograft models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Herein, we identified LNCAROD as a novel METTL3\u2010mediated lncRNA that enhanced radioresistance in ESCC cells and was post\u2010transcriptionally stabilised by YTHDC1. Moreover, we confirmed that LNCAROD prevented ubiquitin\u2010proteasome degradation of PARP1 protein by facilitating PARP1\u2010NPM1 interaction, thereby contributing to homologous recombination\u2010mediated DNA double\u2010strand breaks repair and enhancing the radiation resistance of ESCC cells. Silencing LNCAROD in a nude mouse model of ESCC in vivo resulted in slower tumour growth and increased radiosensitivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings enhance the understanding of m6A\u2010modified lncRNA\u2010driven machinery in ESCC radioresistance and underscore the significance of LNCAROD in this context, thereby contributing to the development of a potential therapeutic target for ESCC patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.70039","type":"journal-article","created":{"date-parts":[[2024,10,5]],"date-time":"2024-10-05T07:39:33Z","timestamp":1728113973000},"source":"Crossref","is-referenced-by-count":24,"title":["N<sup>6<\/sup>\u2010methyladenosine\u2010mediated upregulation of LNCAROD confers radioresistance in esophageal squamous cell carcinoma through stabilizing PARP1"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0391-5076","authenticated-orcid":false,"given":"Xiaobo","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"},{"name":"Department of Radiation Oncology The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinran","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shupei","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Peripheral Vascular The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbing","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6973-1923","authenticated-orcid":false,"given":"Xixi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jncc.2023.01.002"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12087"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(17)31462\u20109"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575\u2010021\u201000419\u20103"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010020\u201000450\u2010x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422\u2010022\u201000741\u20108"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1432"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau1646"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.10.015"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.687"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2017.10.001"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010cellbio\u2010100616\u2010060758"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.351"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.06.017"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495\u2010022\u201001784\u20103"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.2147\/ijgm.S333697"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010022\u201003818\u20105"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/5632744"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw104"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2023.216440"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201023501\u20105"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2021.07.007"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1027"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.6"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/jrr\/rrac096"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33918"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.Can\u201022\u20103631"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010med\u2010081313\u2010121208"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010022\u201000535\u20105"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.53"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.Ccr\u201021\u20103843"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010023\u201001839\u20102"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010021\u201002084\u20105"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010022\u201001049\u20101"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878\u20100261.12676"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10142\u2010022\u201000954\u20105"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.045"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40164\u2010023\u201000386\u20102"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15590"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz120"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6437"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201011795\u20105"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201015364\u2010z"}],"container-title":["Clinical and Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.70039","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T12:39:19Z","timestamp":1748349559000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ctm2.70039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":44,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1002\/ctm2.70039"],"URL":"https:\/\/doi.org\/10.1002\/ctm2.70039","archive":["Portico"],"relation":{},"ISSN":["2001-1326","2001-1326"],"issn-type":[{"value":"2001-1326","type":"print"},{"value":"2001-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10]]},"article-number":"e70039"}}