{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:21:55Z","timestamp":1791379315680,"version":"4.3.2"},"reference-count":50,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"unspecified","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["21ZR1414300"],"award-info":[{"award-number":["21ZR1414300"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874115"],"award-info":[{"award-number":["81874115"]}],"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":["82002795"],"award-info":[{"award-number":["82002795"]}],"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":["82072919"],"award-info":[{"award-number":["82072919"]}],"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":["82173274"],"award-info":[{"award-number":["82173274"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2022,9,22]]},"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Despite the success of HER2-targeted therapy in achieving prolonged survival in approximately 50% of treated individuals, treatment resistance is still an important challenge for HER2+ breast cancer (BC) patients. The influence of both adaptive and innate immune responses on the therapeutic outcomes of HER2+BC patients has been extensively demonstrated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Long non-coding RNAs expressed in non-pathological complete response (pCR) HER2 positive BC were screened and validated by RNA-seq. Survival analysis were made by Kaplan-Meier method. Cell death assay and proliferation assay were performed to confirm the phenotype of LINC00624. RT-qPCR and western blot were used to assay the IFN response. Xenograft mouse model were used for in vivo confirmation of anti-neu treatment resistance. RNA pull-down and immunoblot were used to confirm the interaction of ADAR1 and LINC00624. ADAR1 recombinant protein were purified from baculovirus expression system. B16-OVA cells were used to study antigen presentation both in vitro and in vivo. Flow cytometry was used to determine the tumor infiltrated immune cells of xenograft model. Antisense oligonucleotides (ASOs) were used for in vivo treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In this study, we found that LINC00624 blocked the antitumor effect of HER2- targeted therapy both in vitro and in vivo by inhibiting type I interferon (IFN) pathway activation. The double-stranded RNA-like structure of LINC00624 can bind and be edited by the adenosine (A) to inosine (I) RNA-editing enzyme adenosine deaminase RNA specific 1 (ADAR1), and this editing has been shown to release the growth inhibition and attenuate the innate immune response caused by the IFN response. Notably, LINC00624 promoted the stabilization of ADAR1 by inhibiting its ubiquitination-induced degradation triggered by \u03b2-TrCP. In contrast, LINC00624 inhibited major histocompatibility complex (MHC) class I antigen presentation and limited CD8+T\u2009cell infiltration in the cancer microenvironment, resulting in immune checkpoint blockade inhibition and anti-HER2 treatment resistance mediated through ADAR1.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In summary, these results suggest that LINC00624 is a cancer immunosuppressive lncRNA and targeting LINC00624 through ASOs in tumors expressing high levels of LINC00624 has great therapeutic potential in future clinical applications.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2022-004666","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T11:12:11Z","timestamp":1666005131000},"page":"e004666","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Immunosuppressive lncRNA LINC00624 promotes tumor progression and therapy resistance through ADAR1 stabilization"],"prefix":"10.1136","volume":"10","author":[{"given":"Qi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingqiu","family":"Xiu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiru","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China"},{"name":"Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China"},{"name":"Department of Breast Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyan","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benlong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Ming","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenglin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China"},{"name":"Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayun","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8103-0505","authenticated-orcid":false,"given":"Jiong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China"},{"name":"Collaborative Innovation Center for Cancer Medicine, Shanghai Medical College, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"2025100306532489000_10.10.e004666.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-018-0011-2"},{"key":"2025100306532489000_10.10.e004666.2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00046-08"},{"key":"2025100306532489000_10.10.e004666.3","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.cell.2017.12.038","article-title":"Human ADAR1 prevents endogenous RNA from triggering translational shutdown","volume":"172","author":"Chung","year":"2018","journal-title":"Cell"},{"key":"2025100306532489000_10.10.e004666.4","doi-asserted-by":"publisher","DOI":"10.1038\/nri3581"},{"key":"2025100306532489000_10.10.e004666.5","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.78"},{"key":"2025100306532489000_10.10.e004666.6","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02357-4"},{"key":"2025100306532489000_10.10.e004666.7","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.trecan.2019.03.004","article-title":"ADAR and immune silencing in cancer","volume":"5","author":"Herbert","year":"2019","journal-title":"Trends Cancer"},{"key":"2025100306532489000_10.10.e004666.8","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3708"},{"key":"2025100306532489000_10.10.e004666.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-019-0352-z"},{"key":"2025100306532489000_10.10.e004666.10","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-16-0177"},{"key":"2025100306532489000_10.10.e004666.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-020-00322-0"},{"key":"2025100306532489000_10.10.e004666.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2017.11.018"},{"key":"2025100306532489000_10.10.e004666.13","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.TM118.004166"},{"key":"2025100306532489000_10.10.e004666.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0768-9"},{"key":"2025100306532489000_10.10.e004666.15","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1732"},{"key":"2025100306532489000_10.10.e004666.16","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djk134"},{"key":"2025100306532489000_10.10.e004666.17","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ejca.2021.06.026","article-title":"The role of tyrosine kinase inhibitors in the treatment of HER2+ metastatic breast cancer","volume":"154","author":"Le Du","year":"2021","journal-title":"Eur J Cancer"},{"key":"2025100306532489000_10.10.e004666.18","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-2522-2"},{"key":"2025100306532489000_10.10.e004666.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2010.06.014"},{"key":"2025100306532489000_10.10.e004666.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2011.12.013"},{"key":"2025100306532489000_10.10.e004666.21","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/S1470-2045(16)30631-3","article-title":"Tumour-infiltrating lymphocytes in advanced HER2-positive breast cancer treated with pertuzumab or placebo in addition to trastuzumab and docetaxel: a retrospective analysis of the CLEOPATRA study","volume":"18","author":"Luen","year":"2017","journal-title":"Lancet Oncol"},{"key":"2025100306532489000_10.10.e004666.22","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr209"},{"key":"2025100306532489000_10.10.e004666.23","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt006"},{"key":"2025100306532489000_10.10.e004666.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14802-2"},{"key":"2025100306532489000_10.10.e004666.25","doi-asserted-by":"publisher","DOI":"10.1038\/nature04734"},{"key":"2025100306532489000_10.10.e004666.26","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-3283"},{"key":"2025100306532489000_10.10.e004666.27","doi-asserted-by":"publisher","DOI":"10.1038\/nature24041"},{"key":"2025100306532489000_10.10.e004666.28","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1002\/hep.31530","article-title":"Gain of LINC00624 enhances liver cancer progression by disrupting the histone deacetylase 6\/Tripartite motif containing 28\/Zinc finger protein 354C corepressor complex","volume":"73","author":"Li","year":"2021","journal-title":"Hepatology"},{"key":"2025100306532489000_10.10.e004666.29","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn188"},{"key":"2025100306532489000_10.10.e004666.30","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611392200"},{"key":"2025100306532489000_10.10.e004666.31","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1128\/jvi.70.3.1961-1968.1996","article-title":"Mechanism of interferon action: functionally distinct RNA-binding and catalytic domains in the interferon-inducible, double-stranded RNA-specific adenosine deaminase","volume":"70","author":"Liu","year":"1996","journal-title":"J Virol"},{"key":"2025100306532489000_10.10.e004666.32","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa532"},{"key":"2025100306532489000_10.10.e004666.33","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky800"},{"key":"2025100306532489000_10.10.e004666.34","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0610-9"},{"key":"2025100306532489000_10.10.e004666.35","doi-asserted-by":"crossref","first-page":"5849","DOI":"10.1093\/nar\/gkaa305","article-title":"The cell line A-to-I RNA editing catalogue","volume":"48","author":"Schaffer","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"2025100306532489000_10.10.e004666.36","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.737098"},{"key":"2025100306532489000_10.10.e004666.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.04.023"},{"key":"2025100306532489000_10.10.e004666.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2015.03.004"},{"key":"2025100306532489000_10.10.e004666.39","article-title":"Tumor immunological phenotype signature-based high-throughput screening for the discovery of combination immunotherapy compounds","volume":"7","author":"Wang","year":"2021","journal-title":"Sci Adv"},{"key":"2025100306532489000_10.10.e004666.40","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2911-7"},{"key":"2025100306532489000_10.10.e004666.41","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa2630"},{"key":"2025100306532489000_10.10.e004666.42","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a028555","article-title":"Responses to cytokines and interferons that depend upon JAKs and STATs","volume":"10","author":"Stark","year":"2018","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"2025100306532489000_10.10.e004666.43","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032713-120231"},{"key":"2025100306532489000_10.10.e004666.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2013.04.002"},{"key":"2025100306532489000_10.10.e004666.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2016.01.010"},{"key":"2025100306532489000_10.10.e004666.46","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-19-0545"},{"key":"2025100306532489000_10.10.e004666.47","doi-asserted-by":"publisher","DOI":"10.1172\/JCI123540"},{"key":"2025100306532489000_10.10.e004666.48","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gky1228","article-title":"Sensitive ADAR editing reporter in cancer cells enables high-throughput screening of small molecule libraries","volume":"47","author":"Fritzell","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2025100306532489000_10.10.e004666.49","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1038\/s41423-021-00729-1","article-title":"Hepatitis B virus evades immune recognition via RNA adenosine deaminase ADAR1-mediated viral RNA editing in hepatocytes","volume":"18","author":"Wang","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"2025100306532489000_10.10.e004666.50","doi-asserted-by":"publisher","DOI":"10.1038\/nature23465"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2022-004666","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T13:53:36Z","timestamp":1759499616000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2022-004666"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10]]},"references-count":50,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10,17]]},"published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1136\/jitc-2022-004666"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2022-004666","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10]]}}}