{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:50:24Z","timestamp":1791219024591,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T00:00:00Z","timestamp":1682380800000},"content-version":"vor","delay-in-days":0,"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":["82203809"],"award-info":[{"award-number":["82203809"]}],"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":["81372327"],"award-info":[{"award-number":["81372327"]}],"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":["81572427"],"award-info":[{"award-number":["81572427"]}],"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":["81874189"],"award-info":[{"award-number":["81874189"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFA0208904"],"award-info":[{"award-number":["2018YFA0208904"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bone is the second leading metastatic site for hepatocellular carcinoma (HCC). Patients with HCC and bone metastasis suffer poor quality of life and reduced survival time. Extracellular vesicles (EVs) are widely involved in HCC formation and metastasis. However, the communication between primary HCC and bone lesions mediated by EVs remains unclear and the possible effect of bone metastasis on the progression of HCC remains largely unknown. Here, bone\u2010metastasized HCC\u2010derived EVs (BM\u2010EVs) are found to localize to orthotropic HCC cells and promote HCC progression. Mechanistically, miR\u20103190\u20105p (miR\u20103190) is upregulated in intracellular HCC cells isolated from bone lesions as well as in their derived EVs. miR\u20103190 in BM\u2010EVs is transferred into orthotopic tumor cells and enhances their metastatic capacity by downregulating AlkB homolog 5 (<jats:italic>ALKBH5<\/jats:italic>) expression. Decreased level of <jats:italic>ALKBH5<\/jats:italic> exacerbates the prometastatic characteristics of HCC by modulating gene expression in N6\u2010methyladenosine\u2010dependent and \u2010independent ways. Finally, antagomir\u2010miR\u20103190\u2010loaded liposomes with HCC affinity successfully suppress HCC progression in mice treated with BM\u2010EVs. These findings reveal that BM\u2010EVs initiate prometastatic cascades in orthotopic HCC by transferring ALKBH5\u2010targeting miR\u20103190 and miR\u20103190 is serving as a promising therapeutic target for inhibiting the progression of HCC in patients with bone metastasis.<\/jats:p>","DOI":"10.1002\/advs.202207080","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T07:48:11Z","timestamp":1682408891000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Bone Lesion\u2010Derived Extracellular Vesicles Fuel Prometastatic Cascades in Hepatocellular Carcinoma by Transferring ALKBH5\u2010Targeting miR\u20103190\u20105p"],"prefix":"10.1002","volume":"10","author":[{"given":"Shenqi","family":"Han","sequence":"first","affiliation":[{"name":"Hepatic Surgery Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"},{"name":"Clinical Medical Research Center of Hepatic Surgery at Hubei Province  Wuhan 430030 China"},{"name":"Hubei Key Laboratory of Hepato\u2010Pancreatic\u2010Biliary Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Xue","sequence":"additional","affiliation":[{"name":"Hepatic Surgery Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"},{"name":"Clinical Medical Research Center of Hepatic Surgery at Hubei Province  Wuhan 430030 China"},{"name":"Hubei Key Laboratory of Hepato\u2010Pancreatic\u2010Biliary Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wei","sequence":"additional","affiliation":[{"name":"Hepatic Surgery Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"},{"name":"Clinical Medical Research Center of Hepatic Surgery at Hubei Province  Wuhan 430030 China"},{"name":"Hubei Key Laboratory of Hepato\u2010Pancreatic\u2010Biliary Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuying","family":"Yong","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Nanomedicine College of Life Science and Technology Huazhong University of Science and Technology  Wuhan 430074 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlong","family":"Jia","sequence":"additional","affiliation":[{"name":"Hepatic Surgery Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"},{"name":"Clinical Medical Research Center of Hepatic Surgery at Hubei Province  Wuhan 430030 China"},{"name":"Hubei Key Laboratory of Hepato\u2010Pancreatic\u2010Biliary Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqiang","family":"Qi","sequence":"additional","affiliation":[{"name":"Hepatic Surgery Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"},{"name":"Clinical Medical Research Center of Hepatic Surgery at Hubei Province  Wuhan 430030 China"},{"name":"Hubei Key Laboratory of Hepato\u2010Pancreatic\u2010Biliary Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Luo","sequence":"additional","affiliation":[{"name":"Hepatic Surgery Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"},{"name":"Clinical Medical Research Center of Hepatic Surgery at Hubei Province  Wuhan 430030 China"},{"name":"Hubei Key Laboratory of Hepato\u2010Pancreatic\u2010Biliary Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junnan","family":"Liang","sequence":"additional","affiliation":[{"name":"Hepatic Surgery Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"},{"name":"Clinical Medical Research Center of Hepatic Surgery at Hubei Province  Wuhan 430030 China"},{"name":"Hubei Key Laboratory of Hepato\u2010Pancreatic\u2010Biliary Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyuan","family":"Wen","sequence":"additional","affiliation":[{"name":"Hepatic Surgery Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"},{"name":"Clinical Medical Research Center of Hepatic Surgery at Hubei Province  Wuhan 430030 China"},{"name":"Hubei Key Laboratory of Hepato\u2010Pancreatic\u2010Biliary Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Bie","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Nanomedicine College of Life Science and Technology Huazhong University of Science and Technology  Wuhan 430074 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifang","family":"Liang","sequence":"additional","affiliation":[{"name":"Hepatic Surgery Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"},{"name":"Clinical Medical Research Center of Hepatic Surgery at Hubei Province  Wuhan 430030 China"},{"name":"Hubei Key Laboratory of Hepato\u2010Pancreatic\u2010Biliary Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiumeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Hepatic Surgery Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"},{"name":"Clinical Medical Research Center of Hepatic Surgery at Hubei Province  Wuhan 430030 China"},{"name":"Hubei Key Laboratory of Hepato\u2010Pancreatic\u2010Biliary Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyang","family":"Ding","sequence":"additional","affiliation":[{"name":"Hepatic Surgery Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"},{"name":"Clinical Medical Research Center of Hepatic Surgery at Hubei Province  Wuhan 430030 China"},{"name":"Hubei Key Laboratory of Hepato\u2010Pancreatic\u2010Biliary Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangliang","family":"Yang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Nanomedicine College of Life Science and Technology Huazhong University of Science and Technology  Wuhan 430074 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Gan","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Nanomedicine College of Life Science and Technology Huazhong University of Science and Technology  Wuhan 430074 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1151-4942","authenticated-orcid":false,"given":"Zhao","family":"Huang","sequence":"additional","affiliation":[{"name":"Hepatic Surgery Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"},{"name":"Clinical Medical Research Center of Hepatic Surgery at Hubei Province  Wuhan 430030 China"},{"name":"Hubei Key Laboratory of Hepato\u2010Pancreatic\u2010Biliary Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Chen","sequence":"additional","affiliation":[{"name":"Hepatic Surgery Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"},{"name":"Clinical Medical Research Center of Hepatic Surgery at Hubei Province  Wuhan 430030 China"},{"name":"Hubei Key Laboratory of Hepato\u2010Pancreatic\u2010Biliary Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"},{"name":"Key Laboratory of Organ Transplantation Ministry of Education  Wuhan 430030 China"},{"name":"Key Laboratory of Organ Transplantation National Health Commission  Wuhan 430030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1609-7260","authenticated-orcid":false,"given":"Bixiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hepatic Surgery Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"},{"name":"Clinical Medical Research Center of Hepatic Surgery at Hubei Province  Wuhan 430030 China"},{"name":"Hubei Key Laboratory of Hepato\u2010Pancreatic\u2010Biliary Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"},{"name":"Key Laboratory of Organ Transplantation Ministry of Education  Wuhan 430030 China"},{"name":"Key Laboratory of Organ Transplantation National Health Commission  Wuhan 430030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,25]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-00216-3"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI143764"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.10.005"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.03.011"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-021-00406-5"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31673"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202001961"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-022-0928-z"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-013-9454-4"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm4081600"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.55795"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.02.006"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-018-4861-x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12175"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.04.011"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.07.014"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02583-0"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.03.004"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.10.015"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05386-4"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-022-00370-2"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01239-w"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-021-08449-5"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.70149"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-019-1159-2"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2004.05.013"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-022-00893-0"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2000"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.11.025"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.09.007"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.02.029"},{"key":"e_1_2_9_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.01.043"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11112"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.02.013"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2021.08.009"},{"key":"e_1_2_9_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-021-00835-2"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-020117-043854"},{"key":"e_1_2_9_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.05.007"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1166\/jbn.2018.2619"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau6977"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12125"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15756"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12056"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01224-4"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24300"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105268"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.65308"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-021-00383-9"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-018-0451-6"},{"key":"e_1_2_9_44_1","volume":"67","author":"Campbell J. P.","year":"2012","journal-title":"J. Visualized Exp."}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202207080","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T16:53:30Z","timestamp":1759769610000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202207080"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,25]]},"references-count":50,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/advs.202207080"],"URL":"https:\/\/doi.org\/10.1002\/advs.202207080","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,25]]},"assertion":[{"value":"2022-12-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2207080"}}