中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

外泌体在慢性乙型肝炎和HBV相关肝细胞癌发生发展中的作用机制

郭紫薇 陈贺宁 曹旭 张嘉鑫 张宁怡 靳茜 李小科 叶永安

引用本文:
Citation:

外泌体在慢性乙型肝炎和HBV相关肝细胞癌发生发展中的作用机制

DOI: 10.3969/j.issn.1001-5256.2022.09.034
基金项目: 

国家科技重大专项“十三五”课题 (2018ZX10725505)

国家自然科学基金委员会青年科学基金项目 (81804033)

利益冲突声明:所有作者均声明不存在利益冲突。
作者贡献声明:郭紫薇、陈贺宁、曹旭负责设计研究,资料分析,撰写论文;郭紫薇、张嘉鑫、张宁怡、靳茜参与检索文献,数据提取,修改论文;李小科、叶永安负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    李小科,lixiaoke@vip.163.com

    叶永安,yeyongan@vip.163.com

Mechanism of action of exosomes in the development and progression of hepatitis B virus-related chronic hepatitis and hepatocellular carcinoma

Research funding: 

National Science and Technology Major Project '13th Five-Year' (2018ZX10725505);

National Natural Science Foundation of China Youth Science Fund Project (81804033)

More Information
  • 摘要: 外泌体是由细胞内多囊泡体形成,携带脂质、蛋白质、编码和非编码RNA以及线粒体DNA等多种生物大分子,在体内可由包括肝细胞、肝星状细胞和免疫细胞在内的不同细胞类型释放,起着细胞间通讯的作用。越来越多研究表明,外泌体参与了HBV感染导致的慢性乙型肝炎(CHB)及肝细胞癌(HCC)的发生、发展及转归,有望成为HBV感染相关性HCC的早期诊断及预后评估的潜在生物学标志物。本文综述了外泌体在HBV感染宿主过程中的作用及其在CHB和HCC的发生、发展及预后中的重要性,以期为该领域的基础和临床研究提供新思路。

     

  • 图  1  外泌体通讯作用示意图

    Figure  1.  Diagram of exosomes communication

  • [1] ZHANG L, YU D. Exosomes in cancer development, metastasis, and immunity[J]. Biochim Biophys Acta Rev Cancer, 2019, 1871(2): 455-468. DOI: 10.1016/j.bbcan.2019.04.004.
    [2] JOHNSTONE RM, ADAM M, HAMMOND JR, et al. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes)[J]. J Biol Chem, 1987, 262(19): 9412-9420.
    [3] PEGTEL DM, GOULD SJ. Exosomes[J]. Annu Rev Biochem, 2019, 88: 487-514. DOI: 10.1146/annurev-biochem-013118-111902.
    [4] ZHAO L, WANG Y, ZHANG Y. The potential diagnostic and therapeutic applications of exosomes in drug-induced liver injury[J]. Toxicol Lett, 2021, 337: 68-77. DOI: 10.1016/j.toxlet.2020.11.021.
    [5] ZHANG Y, BI J, HUANG J, et al. Exosome: a review of its classification, isolation techniques, storage, diagnostic and targeted therapy applications[J]. Int J Nanomedicine, 2020, 15: 6917-6934. DOI: 10.2147/IJN.S264498.
    [6] KALLURI R, LEBLEU VS. The biology, function, and biomedical applications of exosomes[J]. Science, 2020, 367(6478): eaau6977. DOI: 10.1126/science.aau6977.
    [7] BANG C, THUM T. Exosomes: new players in cell-cell communication[J]. Int J Biochem Cell Biol, 2012, 44(11): 2060-2064. DOI: 10.1016/j.biocel.2012.08.007.
    [8] MASYUK AI, HUANG BQ, WARD CJ, et al. Biliary exosomes influence cholangiocyte regulatory mechanisms and proliferation through interaction with primary cilia[J]. Am J Physiol Gastrointest Liver Physiol, 2010, 299(4): G990-G999. DOI: 10.1152/ajpgi.00093.2010.
    [9] RAPOSO G, STOORVOGEL W. Extracellular vesicles: exosomes, microvesicles, and friends[J]. J Cell Biol, 2013, 200(4): 373-383. DOI: 10.1083/jcb.201211138.
    [10] VALADI H, EKSTRÖM K, BOSSIOS A, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells[J]. Nat Cell Biol, 2007, 9(6): 654-659. DOI: 10.1038/ncb1596.
    [11] KOSAKA N, IGUCHI H, YOSHIOKA Y, et al. Secretory mechanisms and intercellular transfer of microRNAs in living cells[J]. J Biol Chem, 2010, 285(23): 17442-17452. DOI: 10.1074/jbc.M110.107821.
    [12] ISAAC R, REIS F, YING W, et al. Exosomes as mediators of intercellular crosstalk in metabolism[J]. Cell Metab, 2021, 33(9): 1744-1762. DOI: 10.1016/j.cmet.2021.08.006.
    [13] BUKONG TN, MOMEN-HERAVI F, KODYS K, et al. Exosomes from hepatitis C infected patients transmit HCV infection and contain replication competent viral RNA in complex with Ago2-miR122-HSP90[J]. PLoS Pathog, 2014, 10(10): e1004424. DOI: 10.1371/journal.ppat.1004424.
    [14] DREUX M, GARAIGORTA U, BOYD B, et al. Short-range exosomal transfer of viral RNA from infected cells to plasmacytoid dendritic cells triggers innate immunity[J]. Cell Host Microbe, 2012, 12(4): 558-570. DOI: 10.1016/j.chom.2012.08.010.
    [15] DARGAN DJ, SUBAK-SHARPE JH. The effect of herpes simplex virus type 1 L-particles on virus entry, replication, and the infectivity of naked herpesvirus DNA[J]. Virology, 1997, 239(2): 378-388. DOI: 10.1006/viro.1997.8893.
    [16] TERRAULT NA, LOK A, MCMAHON BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance[J]. Hepatology, 2018, 67(4): 1560-1599. DOI: 10.1002/hep.29800.
    [17] NI M, ZENG L. Reasearch progress in relationships between miRNA single nucleotide polymorphisms and HBV infection-related diseases[J]. J Jilin Univ (Med Edit), 2021, 47(6): 1588-1593. DOI: 10.13481/j.1671-587X.20210633.

    倪盟, 曾雷. miRNA单核苷酸多态性与HBV感染相关疾病关系的研究进展[J]. 吉林大学学报(医学版), 2021, 47(6): 1588-1593. DOI: 10.13481/j.1671-587X.20210633.
    [18] MASYUK AI, MASYUK TV, LARUSSO NF. Exosomes in the pathogenesis, diagnostics and therapeutics of liver diseases[J]. J Hepatol, 2013, 59(3): 621-625. DOI: 10.1016/j.jhep.2013.03.028.
    [19] ZHU YF, YU SX, QIU HJ, et al. Exosomes: another arena for the game between viruses and hosts[J]. Chin J Biotech, 2020, 36(9): 1732-1740. DOI: 10.13345/j.cjb.200039.

    朱依凡, 于少雄, 仇华吉, 等. 外泌体: 病毒与宿主博弈的另一"角斗场"[J]. 生物工程学报, 2020, 36(9): 1732-1740. DOI: 10.13345/j.cjb.200039.
    [20] MECKES DG Jr. Exosomal communication goes viral[J]. J Virol, 2015, 89(10): 5200-5203. DOI: 10.1128/JVI.02470-14.
    [21] ANDERSON MR, KASHANCHI F, JACOBSON S. Exosomes in viral disease[J]. Neurotherapeutics, 2016, 13(3): 535-546. DOI: 10.1007/s13311-016-0450-6.
    [22] LIU J, LIU Q, WANG DM, et al. Correlation between serum exosomal miR-122 and miR-146a expression and HBV-DNA load in patients with chronic hepatitis B[J]. Chin J Difficult Comp Cases, 2020, 19(10): 976-979, 984. DOI: 10.3969/j.issn.1671-6450.2020.10.002.

    刘娇, 刘青, 王大明, 等. 慢性乙型肝炎患者血清外泌体miR-122、miR-146a表达与HBV-DNA载量的相关性[J]. 疑难病杂志, 2020, 19(10): 976-979, 984. DOI: 10.3969/j.issn.1671-6450.2020.10.002.
    [23] SHI Y, DU L, LV D, et al. Exosomal interferon-induced transmembrane protein 2 transmitted to dendritic cells inhibits interferon alpha pathway activation and blocks anti-hepatitis B virus efficacy of exogenous interferon alpha[J]. Hepatology, 2019, 69(6): 2396-2413. DOI: 10.1002/hep.30548.
    [24] YANG Y, HAN Q, HOU Z, et al. Exosomes mediate hepatitis B virus (HBV) transmission and NK-cell dysfunction[J]. Cell Mol Immunol, 2017, 14(5): 465-475. DOI: 10.1038/cmi.2016.24.
    [25] WU W, WU D, YAN W, et al. Interferon-induced macrophage-derived exosomes mediate antiviral activity against hepatitis b virus through miR-574-5p[J]. J Infect Dis, 2021, 223(4): 686-698. DOI: 10.1093/infdis/jiaa399.
    [26] CHEN H, WANG LW, HUANG YQ, et al. Interferon-alpha induces high expression of APOBEC3G and STAT-1 in vitro and in vivo[J]. Int J Mol Sci, 2010, 11(9): 3501-3512. DOI: 10.3390/ijms11093501.
    [27] LI J, LIU K, LIU Y, et al. Exosomes mediate the cell-to-cell transmission of IFN-α-induced antiviral activity[J]. Nat Immunol, 2013, 14(8): 793-803. DOI: 10.1038/ni.2647.
    [28] YAO Z, QIAO Y, LI X, et al. Exosomes exploit the virus entry machinery and pathway to transmit alpha interferon-induced antiviral activity[J]. J Virol, 2018, 92(24): e01578-18. DOI: 10.1128/JVI.01578-18.
    [29] DU KL, SUN XD, XU HX, et al. Research progress of SSS exosomes in virus infection[J]. Int J Virol, 2021, 1(1): 86-88. DOI: 10.3760/cma.j.issn.1673-4092.2021.01.020.

    杜凯丽, 孙晓东, 徐红霞, 等. sss外泌体在病毒感染中的研究进展[J]. 国际病毒学杂志, 2021, 1(1): 86-88. DOI: 10.3760/cma.j.issn.1673-4092.2021.01.020.
    [30] YANG JD, HAINAUT P, GORES GJ, et al. A global view of hepatocellular carcinoma: trends, risk, prevention and management[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(10): 589-604. DOI: 10.1038/s41575-019-0186-y.
    [31] GUO W, GAO Y, LI N, et al. Exosomes: New players in cancer (Review)[J]. Oncol Rep, 2017, 38(2): 665-675. DOI: 10.3892/or.2017.5714.
    [32] CHEN R, XU X, TAO Y, et al. Exosomes in hepatocellular carcinoma: a new horizon[J]. Cell Commun Signal, 2019, 17(1): 1. DOI: 10.1186/s12964-018-0315-1.
    [33] LIU J, REN L, LI S, et al. The biology, function, and applications of exosomes in cancer[J]. Acta Pharm Sin B, 2021, 11(9): 2783-2797. DOI: 10.1016/j.apsb.2021.01.001.
    [34] WANG H, LU Z, ZHAO X. Tumorigenesis, diagnosis, and therapeutic potential of exosomes in liver cancer[J]. J Hematol Oncol, 2019, 12(1): 133. DOI: 10.1186/s13045-019-0806-6.
    [35] YANG X, LI H, SUN H, et al. Hepatitis B virus-encoded microRNA controls viral replication[J]. J Virol, 2017, 91(10): e01919-16. DOI: 10.1128/JVI.01919-16.
    [36] KOGURE T, LIN WL, YAN IK, et al. Intercellular nanovesicle-mediated microRNA transfer: a mechanism of environmental modulation of hepatocellular cancer cell growth[J]. Hepatology, 2011, 54(4): 1237-1248. DOI: 10.1002/hep.24504.
    [37] WANG S, XU M, LI X, et al. Exosomes released by hepatocarcinoma cells endow adipocytes with tumor-promoting properties[J]. J Hematol Oncol, 2018, 11(1): 82. DOI: 10.1186/s13045-018-0625-1.
    [38] HE M, QIN H, POON TC, et al. Hepatocellular carcinoma-derived exosomes promote motility of immortalized hepatocyte through transfer of oncogenic proteins and RNAs[J]. Carcinogenesis, 2015, 36(9): 1008-1018. DOI: 10.1093/carcin/bgv081.
    [39] ZHANG H, DENG T, GE S, et al. Exosome circRNA secreted from adipocytes promotes the growth of hepatocellular carcinoma by targeting deubiquitination-related USP7[J]. Oncogene, 2019, 38(15): 2844-2859. DOI: 10.1038/s41388-018-0619-z.
    [40] LIN XJ, FANG JH, YANG XJ, et al. Hepatocellular carcinoma cell-secreted exosomal MicroRNA-210 promotes angiogenesis in vitro and in vivo[J]. Mol Ther Nucleic Acids, 2018, 11: 243-252. DOI: 10.1016/j.omtn.2018.02.014.
    [41] YUKAWA H, SUZUKI K, AOKI K, et al. Imaging of angiogenesis of human umbilical vein endothelial cells by uptake of exosomes secreted from hepatocellular carcinoma cells[J]. Sci Rep, 2018, 8(1): 6765. DOI: 10.1038/s41598-018-24563-0.
    [42] FANG JH, ZHANG ZJ, SHANG LR, et al. Hepatoma cell-secreted exosomal microRNA-103 increases vascular permeability and promotes metastasis by targeting junction proteins[J]. Hepatology, 2018, 68(4): 1459-1475. DOI: 10.1002/hep.29920.
    [43] LI R, WANG Y, ZHANG X, et al. Exosome-mediated secretion of LOXL4 promotes hepatocellular carcinoma cell invasion and metastasis[J]. Mol Cancer, 2019, 18(1): 18. DOI: 10.1186/s12943-019-0948-8.
    [44] FORNER A, REIG M, BRUIX J. Hepatocellular carcinoma[J]. Lancet, 2018, 391(10127): 1301-1314. DOI: 10.1016/S0140-6736(18)30010-2.
    [45] MA F, VAYALIL J, LEE G, et al. Emerging role of tumor-derived extracellular vesicles in T cell suppression and dysfunction in the tumor microenvironment[J]. J Immunother Cancer, 2021, 9(10): e003217. DOI: 10.1136/jitc-2021-003217.
    [46] PATHANIA AS, PRATHIPATI P, CHALLAGUNDLA KB. New insights into exosome mediated tumor-immune escape: Clinical perspectives and therapeutic strategies[J]. Biochim Biophys Acta Rev Cancer, 2021, 1876(2): 188624. DOI: 10.1016/j.bbcan.2021.188624.
    [47] YE L, ZHANG Q, CHENG Y, et al. Tumor-derived exosomal HMGB1 fosters hepatocellular carcinoma immune evasion by promoting TIM-1+ regulatory B cell expansion[J]. J Immunother Cancer, 2018, 6(1): 145. DOI: 10.1186/s40425-018-0451-6.
    [48] MAO X, XU J, WANG W, et al. Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives[J]. Mol Cancer, 2021, 20(1): 131. DOI: 10.1186/s12943-021-01428-1.
    [49] XI L, PENG M, LIU S, et al. Hypoxia-stimulated ATM activation regulates autophagy-associated exosome release from cancer-associated fibroblasts to promote cancer cell invasion[J]. J Extracell Vesicles, 2021, 10(11): e12146. DOI: 10.1002/jev2.12146.
    [50] CHEN Y, MCANDREWS KM, KALLURI R. Clinical and therapeutic relevance of cancer-associated fibroblasts[J]. Nat Rev Clin Oncol, 2021, 18(12): 792-804. DOI: 10.1038/s41571-021-00546-5.
    [51] LIU Z, YOU Y, CHEN Q, et al. Extracellular vesicle-mediated communication between hepatocytes and natural killer cells promotes hepatocellular tumorigenesis[J]. Mol Ther, 2022, 30(2): 606-620. DOI: 10.1016/j.ymthe.2021.07.015.
    [52] KOUWAKI T, OKAMOTO M, TSUKAMOTO H, et al. Extracellular vesicles deliver host and virus RNA and regulate innate immune response[J]. Int J Mol Sci, 2017, 18(3): 666. DOI: 10.3390/ijms18030666.
  • 加载中
图(1)
计量
  • 文章访问数:  406
  • HTML全文浏览量:  110
  • PDF下载量:  44
  • 被引次数: 0
出版历程
  • 收稿日期:  2022-01-13
  • 录用日期:  2022-02-17
  • 出版日期:  2022-09-20
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回