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Bone Lesion-Derived Extracellular Vesicles Fuel Prometastatic Cascades in Hepatocellular Carcinoma by Transferring ALKBH5-Targeting miR-3190-5p

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收录情况： ◇ SCIE

作者：
Han Shenqi[1,2,3] * ; Xue Lin[1,2,3] * ; Wei Yi[1,2,3] * ; Yong Tuying[4] * ; Jia Wenlong[1,2,3] ; Qi Yongqiang[1,2,3] ; Luo Yiming[1,2,3] ; Liang Junnan[1,2,3] ; Wen Jingyuan[1,2,3] ; Bie Nana[4] ; Liang Huifang[1,2,3] ; Liu Qiumeng[1,2,3] ; Ding Zeyang[1,2,3] ; Yang Xiangliang[4] ; Gan Lu[4] ; Huang Zhao[1,2,3] ; Chen Xiaoping[1,2,3,5,6,7] ; Zhang Bixiang[1,2,3,5,6,7] ;
单位： [1]Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. [2]Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, 430030, China. [3]Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. [4]National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China. [5]Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, 430030, China. [6]Key Laboratory of Organ Transplantation, National Health Commission, Wuhan, 430030, China. [7]Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, 430030, China.
出处：
DOI： 10.1002/advs.202207080
ISSN：

关键词： aptamer/liposome bone metastasis bone-liver axis exosome liver cancer

摘要：
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-metastasized HCC-derived EVs (BM-EVs) are found to localize to orthotropic HCC cells and promote HCC progression. Mechanistically, miR-3190-5p (miR-3190) is upregulated in intracellular HCC cells isolated from bone lesions as well as in their derived EVs. miR-3190 in BM-EVs is transferred into orthotopic tumor cells and enhances their metastatic capacity by downregulating AlkB homolog 5 (ALKBH5) expression. Decreased level of ALKBH5 exacerbates the prometastatic characteristics of HCC by modulating gene expression in N6-methyladenosine-dependent and -independent ways. Finally, antagomir-miR-3190-loaded liposomes with HCC affinity successfully suppress HCC progression in mice treated with BM-EVs. These findings reveal that BM-EVs initiate prometastatic cascades in orthotopic HCC by transferring ALKBH5-targeting miR-3190 and miR-3190 is serving as a promising therapeutic target for inhibiting the progression of HCC in patients with bone metastasis.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

基金：
National Natural Science Foundation of China (82203809, 81372327, 81572427, and 81874189), State Key Project on Infection Disease of China (2018ZX10723204-003-003), National Key Research and Development Program of China (2018YFA0208904), Major Technological Innovation Projects of Hubei Province (2018ACA137), and the Fundamental Research Funds for the Central Universities, HUST (5001540006 and 5001540059)
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外文
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中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 材料科学
小类 | 1 区 材料科学：综合 1 区 化学：综合 1 区 纳米科技
最新[2025]版：
大类 | 1 区 综合性期刊
小类 | 1 区 化学：综合 1 区 材料科学：综合 1 区 纳米科技
JCR分区：
出版当年[2021]版：
Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY
最新[2023]版：
Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者单位： [1]Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. [2]Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, 430030, China. [3]Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
共同第一作者：
通讯作者：
通讯机构： [1]Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. [2]Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, 430030, China. [3]Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. [5]Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, 430030, China. [6]Key Laboratory of Organ Transplantation, National Health Commission, Wuhan, 430030, China. [7]Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, 430030, China.
推荐引用方式(GB/T 7714)：
Han Shenqi,Xue Lin,Wei Yi,et al.Bone Lesion-Derived Extracellular Vesicles Fuel Prometastatic Cascades in Hepatocellular Carcinoma by Transferring ALKBH5-Targeting miR-3190-5p[J].ADVANCED SCIENCE.2023,10(17):doi:10.1002/advs.202207080.
APA：
Han Shenqi,Xue Lin,Wei Yi,Yong Tuying,Jia Wenlong...&Zhang Bixiang.(2023).Bone Lesion-Derived Extracellular Vesicles Fuel Prometastatic Cascades in Hepatocellular Carcinoma by Transferring ALKBH5-Targeting miR-3190-5p.ADVANCED SCIENCE,10,(17)
MLA：
Han Shenqi,et al."Bone Lesion-Derived Extracellular Vesicles Fuel Prometastatic Cascades in Hepatocellular Carcinoma by Transferring ALKBH5-Targeting miR-3190-5p".ADVANCED SCIENCE 10..17(2023)

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