中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 39 Issue 2
Feb.  2023
Turn off MathJax
Article Contents

From viral hepatitis to hepatocellular carcinoma: The role of exosomal microRNAs

DOI: 10.3969/j.issn.1001-5256.2023.02.030
Research funding:

National Natural Science Foundation of China (82170541);

Natural Science Foundation of Beijing (7202071)

More Information
  • Corresponding author: WEI Hongshan, drwei@ccmu.edu.cn (ORCID: 0000-0001-8893-653X)
  • Received Date: 2022-06-28
  • Accepted Date: 2022-07-27
  • Published Date: 2023-02-20
  • Exosomes are nano-sized phospholipid bilayer vesicles containing abundant and complex biomolecules, such as DNA, mRNAs, microRNAs (miRNAs), lipids, and proteins. Exosomes can be secreted and ingested by most types of cells to transfer information through intercellular transport. After uptake by recipient cells, exosomes release bioactive substances to regulate the biological processes of recipient cells, such as promoting tumor growth and metastasis. Changes of exosomes and their contents are associated with a variety of diseases. In recent years, the role of exosomal miRNAs in the development and progression of hepatocellular carcinoma (HCC) caused by viral hepatitis has attracted wide attention, and exosomal miRNAs from different sources play different roles in this process. This article briefly reviews the research on the role of exosomal miRNAs in the development and progression of viral hepatitis-related HCC and proposes that exosomal miRNAs may be the targets for immunotherapy for HCC microenvironment.

     

  • loading
  • [1]
    PAN BT, JOHNSTONE RM. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor[J]. Cell, 1983, 33(3): 967-978. DOI: 10.1016/0092-8674(83)90040-5.
    [2]
    SIMONS M, RAPOSO G. Exosomes--vesicular carriers for intercellular communication[J]. Curr Opin Cell Biol, 2009, 21(4): 575-581. DOI: 10.1016/j.ceb.2009.03.007.
    [3]
    AMBROS V. The functions of animal microRNAs[J]. Nature, 2004, 431(7006): 350-355. DOI: 10.1038/nature02871.
    [4]
    LIU R, MA X, CHEN L, et al. MicroRNA-15b suppresses Th17 differentiation and is associated with pathogenesis of multiple sclerosis by targeting O-GlcNAc transferase[J]. J Immunol, 2017, 198(7): 2626-2639. DOI: 10.4049/jimmunol.1601727.
    [5]
    LAKSHMI S, HUGHES TA, PRIYA S. Exosomes and exosomal RNAs in breast cancer: A status update[J]. Eur J Cancer, 2021, 144: 252-268. DOI: 10.1016/j.ejca.2020.11.033.
    [6]
    HENNING RJ. Cardiovascular exosomes and MicroRNAs in cardiovascular physiology and pathophysiology[J]. J Cardiovasc Transl Res, 2021, 14(2): 195-212. DOI: 10.1007/s12265-020-10040-5.
    [7]
    THÉRY C, ZITVOGEL L, AMIGORENA S. Exosomes: composition, biogenesis and function[J]. Nat Rev Immunol, 2002, 2(8): 569-579. DOI: 10.1038/nri855.
    [8]
    KALLURI R, LEBLEU VS. The biology, function, and biomedical applications of exosomes[J]. Science, 2020, 367(6478): eaau6977. DOI: 10.1126/science.aau6977.
    [9]
    LI X, LI C, ZHANG L, et al. The significance of exosomes in the development and treatment of hepatocellular carcinoma[J]. Mol Cancer, 2020, 19(1): 1. DOI: 10.1186/s12943-019-1085-0.
    [10]
    LI C, ZHOU T, CHEN J, et al. The role of Exosomal miRNAs in cancer[J]. J Transl Med, 2022, 20(1): 6. DOI: 10.1186/s12967-021-03215-4.
    [11]
    CHAHAR HS, BAO X, CASOLA A. Exosomes and their role in the life cycle and pathogenesis of RNA viruses[J]. Viruses, 2015, 7(6): 3204-3225. DOI: 10.3390/v7062770.
    [12]
    JIANG W, MA P, DENG L, et al. Hepatitis A virus structural protein pX interacts with ALIX and promotes the secretion of virions and foreign proteins through exosome-like vesicles[J]. J Extracell Vesicles, 2020, 9(1): 1716513. DOI: 10.1080/20013078.2020.1716513.
    [13]
    ZHANG GL, LI YX, ZHENG SQ, et al. Suppression of hepatitis B virus replication by microRNA-199a-3p and microRNA-210[J]. Antiviral Res, 2010, 88(2): 169-175. DOI: 10.1016/j.antiviral.2010.08.008.
    [14]
    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.
    [15]
    RAMAKRISHNAIAH V, THUMANN C, FOFANA I, et al. Exosome-mediated transmission of hepatitis C virus between human hepatoma Huh7.5 cells[J]. Proc Natl Acad Sci U S A, 2013, 110(32): 13109-13113. DOI: 10.1073/pnas.1221899110.
    [16]
    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.
    [17]
    THAKURI B KC, ZHANG J, ZHAO J, et al. HCV-associated exosomes upregulate RUNXOR and RUNX1 expressions to promote MDSC expansion and suppressive functions through STAT3-miR124 axis[J]. Cells, 2020, 9(12): 2715. DOI: 10.3390/cells9122715.
    [18]
    ZHOU Y, WANG X, SUN L, et al. Toll-like receptor 3-activated macrophages confer anti-HCV activity to hepatocytes through exosomes[J]. FASEB J, 2016, 30(12): 4132-4140. DOI: 10.1096/fj.201600696R.
    [19]
    CHEN L, CHEN R, KEMPER S, et al. Suppression of fibrogenic signaling in hepatic stellate cells by Twist1-dependent microRNA-214 expression: Role of exosomes in horizontal transfer of Twist1[J]. Am J Physiol Gastrointest Liver Physiol, 2015, 309(6): G491-G499. DOI: 10.1152/ajpgi.00140.2015.
    [20]
    CHEN L, CHEN R, VELAZQUEZ VM, et al. Fibrogenic signaling is suppressed in hepatic stellate cells through targeting of connective tissue growth factor (CCN2) by cellular or exosomal microRNA-199a-5p[J]. Am J Pathol, 2016, 186(11): 2921-2933. DOI: 10.1016/j.ajpath.2016.07.011.
    [21]
    LEE YS, KIM SY, KO E, et al. Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells[J]. Sci Rep, 2017, 7(1): 3710. DOI: 10.1038/s41598-017-03389-2.
    [22]
    QU Y, ZHANG Q, CAI X, et al. Exosomes derived from miR-181-5p-modified adipose-derived mesenchymal stem cells prevent liver fibrosis via autophagy activation[J]. J Cell Mol Med, 2017, 21(10): 2491-2502. DOI: 10.1111/jcmm.13170.
    [23]
    SUN C, SHI C, DUAN X, et al. Exosomal microRNA-618 derived from mesenchymal stem cells attenuate the progression of hepatic fibrosis by targeting Smad4[J]. Bioengineered, 2022, 13(3): 5915-5927. DOI: 10.1080/21655979.2021.2023799.
    [24]
    KIM JH, LEE CH, LEE SW. Exosomal transmission of MicroRNA from HCV replicating cells stimulates transdifferentiation in hepatic stellate cells[J]. Mol Ther Nucleic Acids, 2019, 14: 483-497. DOI: 10.1016/j.omtn.2019.01.006.
    [25]
    CHALLAGUNDLA KB, WISE PM, Neviani P, et al. Exosome-mediated transfer of microRNAs within the tumor microenvironment and neuroblastoma resistance to chemotherapy[J]. J Natl Cancer Inst, 2015, 107(7): djv135. DOI: 10.1093/jnci/djv135.
    [26]
    BOVY N, BLOMME B, FRÈRES P, et al. Endothelial exosomes contribute to the antitumor response during breast cancer neoadjuvant chemotherapy via microRNA transfer[J]. Oncotarget, 2015, 6(12): 10253-10266. DOI: 10.18632/oncotarget.3520.
    [27]
    ZHANG X, CHEN F, HUANG P, et al. Exosome-depleted MiR-148a-3p derived from hepatic stellate cells promotes tumor progression via ITGA5/PI3K/Akt axis in hepatocellular carcinoma[J]. Int J Biol Sci, 2022, 18(6): 2249-2260. DOI: 10.7150/ijbs.66184.
    [28]
    CHEN C, LUO F, LIU X, et al. NF-kB-regulated exosomal miR-155 promotes the inflammation associated with arsenite carcinogenesis[J]. Cancer Lett, 2017, 388: 21-33. DOI: 10.1016/j.canlet.2016.11.027.
    [29]
    AFFO S, YU LX, SCHWABE RF. The role of cancer-associated fibroblasts and fibrosis in liver cancer[J]. Annu Rev Pathol, 2017, 12: 153-186. DOI: 10.1146/annurev-pathol-052016-100322.
    [30]
    ZHOU Y, REN H, DAI B, et al. Hepatocellular carcinoma-derived exosomal miRNA-21 contributes to tumor progression by converting hepatocyte stellate cells to cancer-associated fibroblasts[J]. J Exp Clin Cancer Res, 2018, 37(1): 324. DOI: 10.1186/s13046-018-0965-2.
    [31]
    FANG T, LV H, LV G, et al. Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer[J]. Nat Commun, 2018, 9(1): 191. DOI: 10.1038/s41467-017-02583-0.
    [32]
    YANG F, NING Z, MA L, et al. Exosomal miRNAs and miRNA dysregulation in cancer-associated fibroblasts[J]. Mol Cancer, 2017, 16(1): 148. DOI: 10.1186/s12943-017-0718-4.
    [33]
    YUGAWA K, YOSHIZUMI T, MANO Y, et al. Cancer-associated fibroblasts promote hepatocellular carcinoma progression through downregulation of exosomal miR-150-3p[J]. Eur J Surg Oncol, 2021, 47(2): 384-393. DOI: 10.1016/j.ejso.2020.08.002.
    [34]
    XIE F, YUAN Y, XIE L, et al. miRNA-320a inhibits tumor proliferation and invasion by targeting c-Myc in human hepatocellular carcinoma[J]. Onco Targets Ther, 2017, 10: 885-894. DOI: 10.2147/OTT.S122992.
    [35]
    ZHANG Z, LI X, SUN W, et al. Loss of exosomal miR-320a from cancer-associated fibroblasts contributes to HCC proliferation and metastasis[J]. Cancer Lett, 2017, 397: 33-42. DOI: 10.1016/j.canlet.2017.03.004.
    [36]
    LIN Q, ZHOU CR, BAI MJ, et al. Exosome-mediated miRNA delivery promotes liver cancer EMT and metastasis[J]. Am J Transl Res, 2020, 12(3): 1080-1095.
    [37]
    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.
    [38]
    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.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(1)  / Tables(1)

    Article Metrics

    Article views (853) PDF downloads(110) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return