专题笔谈

外泌体蛋白、mRNA及非编码RNA调节肝癌发生和发展的研究进展

  • 程玉鑫 ,
  • 刘亮 ,
  • 董适毓 ,
  • 李胜超 ,
  • 张萌
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  • 河北医科大学第四医院肝胆外科 (石家庄 050011 )
张萌,河北医科大学第四医院外科主任医师兼病区主任,外科学博士,副教授,硕士研究生导师。兼任河北省抗癌协会青年理事会理事、中国抗癌协会肿瘤微创治疗专业委员会青年委员、中国医药教育协会肝胆胰外科专业委员会委员、中国医疗保健国际交流促进会胰腺疾病分会青年学组委员、中国研究型医院学会智能医学专业委员会委员、河北省医学会外科学分会门脉高压学组委员、河北省肿瘤联合会肝脏肿瘤分会常委、河北省抗癌协会老年肿瘤专业委员会常委等学术兼职。研究方向:肝胆胰脾等良恶性疾病,擅长肝胆胰良恶性肿瘤的外科手术治疗。主持或参加河北省卫健委课题或河北省自然科学基金多项,获河北医学科技奖一等奖两项。E-mail:sygdwkzm@163.com

收稿日期: 2023-11-14

  网络出版日期: 2024-04-08

基金资助

2022年政府资助临床医学优秀人才项目(冀财预复(2022)180号)

Research advances in exosomal proteins, mRNA and non⁃coding RNA regulation of Hepatocellular Carcinoma

  • Yuxin CHENG ,
  • Liang LIU ,
  • Shiyu DONG ,
  • Shengchao LI ,
  • Meng ZHANG
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  • Department of Hepatobiliary Surgery,Forth Hospital of Hebei Medical University,Shijiazhuang 050011,China

Received date: 2023-11-14

  Online published: 2024-04-08

摘要

外泌体是一种广泛存在于人体各种体液中的细胞外囊泡,它可以携带包括蛋白、核酸、脂质和代谢产物在内的多种成分。通过这些组分,外泌体可以介导细胞间通讯,进而影响人体内各项细胞生命活动。最近研究发现,外泌体在肝细胞癌(hepatocellular carcinoma, HCC)的发生、发展及耐药等各个环节中发挥着重要的调控作用。其中非编码RNAs作为外泌体重要组分可以参与调节HCC肿瘤微环境,影响肿瘤生长、转移、血管生成、免疫调节等生物学行为,有望成为HCC新的诊断、预后标志物或治疗靶点。本文通过对近五年来外泌体组分在HCC进展中的作用进行综述,期望在HCC的早期诊断、预后及治疗等方面提供参考和新的思路。

本文引用格式

程玉鑫 , 刘亮 , 董适毓 , 李胜超 , 张萌 . 外泌体蛋白、mRNA及非编码RNA调节肝癌发生和发展的研究进展[J]. 实用医学杂志, 2024 , 40(6) : 748 -755 . DOI: 10.3969/j.issn.1006-5725.2024.06.004

Abstract

Exosomes are extracellular vesicles commonly detected in numerous body fluids and contain a variety of components such as proteins, nucleic acids, lipids, and metabolites. These components enable exosomes to mediate intercellular communication and impact diverse cellular processes. Recently, research has highlighted that exosomes have a significant regulatory role in numerous aspects of hepatocellular carcinoma (HCC) occurrence, development, and drug resistance. Non-coding RANs, a crucial component of exosomes, can regulate the HCC tumour microenvironment with a direct impact on biological behaviours such as tumour growth, metastasis, angiogenesis, and immunomodulation. To this end, exosomes present an interesting avenue for further research in the field of HCC therapy. It is anticipated to become a novel diagnostic, prognostic marker, or therapeutic target for hepatocellular carcinoma (HCC). Our review of the role played by exosomal components in HCC progression over the last five years aims to furnish references and innovative perspectives for early diagnosis, prognosis, and treatment of HCC.

参考文献

1 SUNG H, FERLAY J, SIEGEL R L, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries [J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi:10.3322/caac.21660
2 招文, 文彬, 孙嘉, 等. 肝细胞癌中外泌体ncRNAs的研究进展 [J]. 中国药理学通报, 2020, 36(8): 1041-1044.
3 LIU D, SONG T. Changes in and challenges regarding the surgical treatment of hepatocellular carcinoma in China [J]. Biosci Trends, 2021, 15(3): 142-147. doi:10.5582/bst.2021.01083
4 KALLURI R, LEBLEU V S. The biology, function, and biomedical applications of exosomes [J]. Science, 2020, 367(6478): eaau6977. doi:10.1126/science.aau6977
5 SAS Z, CENDROWICZ E, WEINH?USER I, et al. Tumor Microenvironment of Hepatocellular Carcinoma: Challenges and Opportunities for New Treatment Options [J]. Int J Mol Sci, 2022, 23(7): 3778. doi:10.3390/ijms23073778
6 毛元鹏, 于哲, 宋阿倩, 等. 从病毒性肝炎到肝细胞癌:外泌体microRNA的作用 [J] 临床肝胆病杂志, 2023, 39(2): 439-443. doi:10.3969/j.issn.1001-5256.2023.02.030
7 MASHOURI L, YOUSEFI H, AREF A R, et al. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance [J]. Mol Cancer, 2019, 18: 75. doi:10.1186/s12943-019-0991-5
8 ZHANG L, YU D. Exosomes in cancer development, metastasis, and immunity [J]. Biochim Biophys Acta Rev Cancer, 2019, 1871(2):1871(2):455-468. doi:10.1016/j.bbcan.2019.04.004
9 李维特, 杨硕, 乔蕊, 等. 外泌体的生物学特性及其在分子标记中的作用 [J]. 实用医学杂志. 2017, 33(12): 2062-2064. doi:10.3969/j.issn.1006-5725.2017.12.046
10 CHO H J, BAEK G O, YOON M G, et al. Over expressed Proteins in HCC Cell-Derived Exosomes, CCT8, and Cofilin-1 Are Potential Biomakers for Patients with HCC [J]. Diagnostics(Basel),11(7):1221. doi:10.3390/diagnostics11071221
11 HUANG X Y, ZHANG J T, LI F, et al. Exosomal proteomics identifies RAB13 as a potential regulator of metastasis for HCC [J]. Hepatol Commun, 2023, 7(1): e0006. doi:10.1097/hc9.0000000000000006
12 YU B, ZHOU S, LONG D, et al. DDX55 promotes hepatocellular carcinoma progression by interacting with BRD4 and participating in exosome-mediated cell-cell communication [J]. Cancer Sci, 2022, 113(9): 3002-3017. doi:10.1111/cas.15393
13 DAI W, WANG Y, YANG T, et al. Downregulation of exosomal CLEC3B in hepatocellular carcinoma promotes metastasis and angiogenesis via AMPK and VEGF signals [J]. Cell Commun Signal, 2019, 17(1): 113. doi:10.1186/s12964-019-0423-6
14 LI L, ZHAO J, ZHANG Q, et al. Cancer Cell-Derived Exosomes Promote HCC Tumorigenesis Through Hedgehog Pathway [J]. Front Oncol, 2021, 11: 756205. doi:10.3389/fonc.2021.756205
15 IOANNOU M S, MCPHERSON P S. Regulation of Cancer Cell Behavior by the Small GTPase Rab13 [J]. J Biol Chem, 2016,29(19):9929-9937. doi:10.1074/jbc.r116.715193
16 LI M, LU Y, XU Y, et al. Horizontal transfer of exosomal CXCR4 promotes murine hepatocarcinoma cell migration, invasion and lymphangiogenesis [J]. Gene, 2018, 676: 101-109. doi:10.1016/j.gene.2018.07.018
17 SUN H, WANG C, HU B, et al. Exosomal S100A4 derived from highly metastatic hepatocellular carcinoma cells promotes metastasis by activating STAT3[J]. Signal Transduct Target Ther, 2021, 6(1): 187. doi:10.1038/s41392-021-00579-3
18 JIANG K, DONG C, YIN Z, et al. Exosome-derived ENO1 regulates integrin α6β4 expression and promotes hepatocellular carcinoma growth and metastasis [J]. Cell Death Dis, 2020, 11(11): 972. doi:10.1038/s41419-020-03179-1
19 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
20 QIN W, WANG L, TIAN H, et al. CAF-derived exosomes transmitted Gremlin-1 promotes cancer progression and decreases the sensitivity of hepatoma cells to sorafenib[J]. Mol Carcinog, 2022, 61(8): 764-775. doi:10.1002/mc.23416
21 HUANG H, ZHOU Z, LI H, et al. Down-regulation of ER-α36 mRNA in serum exosomes of the patients with hepatocellular carcinoma [J]. Clin Transl Med, 2020, 10(1): 346-352. doi:10.1002/ctm2.18
22 SASAKI K, KOHGO Y, OHTAKE T. Splicing variant of hepcidin mRNA [J]. Vitam Horm, 2019, 110: 131-141. doi:10.1016/bs.vh.2019.01.006
23 GWAD A ABD EL, MATBOLI M, EL-TAWDI A, et al. Role of exosomal competing endogenous RNA in patients with hepatocellular carcinoma [J]. J Cell Biochem, 2018, 119(10): 8600-8610. doi:10.1002/jcb.27109
24 FRüNDT T, KRAUSE L, HUSSEY E, et al. Diagnostic and Prognostic Value of miR-16, miR-146a, miR-192 and miR-221 in Exosomes of Hepatocellular Carcinoma and Liver Cirrhosis Patients [J]. Cancers (Basel), 2021, 13(10):2484. doi:10.3390/cancers13102484
25 RUI T, ZHANG X, GUO J, et al. Serum-Exosome-Derived miRNAs Serve as Promising Biomarkers for HCC Diagnosis [J]. Cancers (Basel), 2022, 15(1):205. doi:10.3390/cancers15010205
26 CUI Y, XU H F, LIU M Y, et al. Mechanism of exosomal microRNA-224 in development of hepatocellular carcinoma and its diagnostic and prognostic value[J]. World J Gastroenterol, 2019, 25(15): 1890-1898. doi:10.3748/wjg.v25.i15.1890
27 TIAN X P, WANG C Y, JIN X H, et al. Acidic Microenvironment Up-Regulates Exosomal miR-21 and miR-10b in Early-Stage Hepatocellular Carcinoma to Promote Cancer Cell Proliferation and Metastasis[J]. Theranostics, 2019, 9(7): 1965-1979. doi:10.7150/thno.30958
28 LIN H, PENG J, ZHU T, et al. Exosomal miR-4800-3p Aggravates the Progression of Hepatocellular Carcinoma via Regulating the Hippo Signaling Pathway by Targeting STK25 [J]. Front Oncol, 2022, 12: 759864. doi:10.3389/fonc.2022.759864
29 YU Y, MIN Z, ZHIHANG Z, et al. Hypoxia-induced exosomes promote hepatocellular carcinoma proliferation and metastasis via miR-1273f transfer [J]. Exp Cell Res, 2019, 385(1): 111649. doi:10.1016/j.yexcr.2019.111649
30 HU Z Q, CHEN J P, ZHAO Y P, et al. Exosomal miR-452-5p Induce M2 Macrophage Polarization to Accelerate Hepatocellular Carcinoma Progression by Targeting TIMP3 [J]. J Immunol Res, 2022, 2022: 1032106. doi:10.1155/2022/1032106
31 LI W, DING X, WANG S, et al. Downregulation of serum exosomal miR-320d predicts poor prognosis in hepatocellular carcinoma [J]. J Clin Lab Anal, 2020, 34(6): e23239. doi:10.1002/jcla.23239
32 GAI X, TANG B, LIU F, et al. mTOR/miR-145-regulated exosomal GOLM1 promotes hepatocellular carcinoma through augmented GSK-3β/MMPs [J]. J Genet Genomics, 2019, 46(5): 235-245. doi:10.1016/j.jgg.2019.03.013
33 BONGOLO C C, THOKERUNGA E, YAN Q, et al. Exosomes Derived from microRNA-27a-3p Overexpressing Mesenchymal Stem Cells Inhibit the Progression of Liver Cancer through Suppression of Golgi Membrane Protein 1 [J]. Stem Cells Int, 2022, 2022: 9748714. doi:10.1155/2022/9748714
34 LI W, XIN X, LI X, et al. Exosomes secreted by M2 macrophages promote cancer stemness of hepatocellular carcinoma via the miR-27a-3p/TXNIP pathways[J]. Int Immunopharmacol, 2021, 101(Pt A): 107585. doi:10.1016/j.intimp.2021.107585
35 LIU Y, TAN J, OU S, et al. Adipose-derived exosomes deliver miR-23a/b to regulate tumor growth in hepatocellular cancer by targeting the VHL/HIF axis [J]. J Physiol Biochem, 2019, 75(3): 391-401. doi:10.1007/s13105-019-00692-6
36 QI Y, WANG H, ZHANG Q, et al. CAF-Released Exosomal miR-20a-5p Facilitates HCC Progression via the LIMA1-Mediated β-Catenin Pathway [J]. Cells, 2022, 11(23):3857. doi:10.3390/cells11233857
37 MA Y S, LIU J B, LIN L, et al. Exosomal microRNA-15a from mesenchymal stem cells impedes hepatocellular carcinoma progression via downregulation of SALL4 [J]. Cell Death Discov, 2021, 7(1): 224. doi:10.1038/s41420-021-00611-z
38 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
39 XU Y, LAI Y, CAO L, et al. Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-451a represses epithelial-mesenchymal transition of hepatocellular carcinoma cells by inhibiting ADAM10 [J]. RNA Biol, 2021, 18(10): 1408-1423. doi:10.1080/15476286.2020.1851540
40 刘 蕊, 刘 涛. 长链非编码RNA在肝细胞癌发生发展及转移和复发中的研究进展 [J]. 重庆医学, 2022, 51(15): 2682-2686,2700. doi:10.3969/j.issn.1671-8348.2022.15.034
41 WANG T, ZHU H, XIAO M, et al. Serum exosomal long noncoding RNA CRNDE as a prognostic biomarker for hepatocellular carcinoma [J]. J Clin Lab Anal, 2021, 35(11): e23959. doi:10.1002/jcla.23959
42 XU Y, LUAN G, LI Z, et al. Tumour-derived exosomal lncRNA SNHG16 induces telocytes to promote metastasis of hepatocellular carcinoma via the miR-942-3p/MMP9 axis [J]. Cell Oncol (Dordr), 2023, 46(2): 251-264. doi:10.1007/s13402-022-00746-w
43 LU L, HUANG J, MO J, et al. Exosomal lncRNA TUG1 from cancer-associated fibroblasts promotes liver cancer cell migration, invasion, and glycolysis by regulating the miR-524-5p/SIX1 axis [J]. Cell Mol Biol Lett, 2022, 27(1): 17. doi:10.1186/s11658-022-00309-9
44 XU M, ZHOU C, WENG J, et al. Tumor associated macro-phages-derived exosomes facilitate hepatocellular carcinoma malignance by transferring lncMMPA to tumor cells and activating glycolysis pathway [J]. J Exp Clin Cancer Res, 2022, 41(1): 253. doi:10.1186/s13046-022-02458-3
45 ZHUO C, YI T, PU J, et al. Exosomal linc-FAM138B from cancer cells alleviates hepatocellular carcinoma progression via regulating miR-765 [J]. Aging (Albany NY), 2020, 12(24): 26236-26247. doi:10.18632/aging.202430
46 WANG X, ZHOU Y, DONG K, et al. Exosomal lncRNA HMMR‐AS1 mediates macrophage polarization through miR ‐147a/ ARID3A axis under hypoxia and affects the progression of hepatocellular carcinoma [J]. Environ Toxicol, 2022, 37(6): 1357-1372. doi:10.1002/tox.23489
47 LI B, MAO R, LIU C, et al. LncRNA FAL1 promotes cell proliferation and migration by acting as a CeRNA of miR-1236 in hepatocellular carcinoma cells. [J]. Life Sci, 2018, 197: 122-129. doi:10.1016/j.lfs.2018.02.006
48 LI S, QI Y, HUANG Y, et al. Exosome-derived SNHG16 sponging miR-4500 activates HUVEC angiogenesis by targeting GALNT1 via PI3K/Akt/mTOR pathway in hepatocellular carcinoma [J]. J Physiol Biochem, 2021, 77(4): 667-682. doi:10.1007/s13105-021-00833-w
49 YOU L N, TAI Q W, XU L, et al. Exosomal LINC00161 promotes angiogenesis and metastasis via regulating miR-590-3p/ROCK axis in hepatocellular carcinoma [J]. Cancer Gene Ther, 2021, 28(6): 719-736. doi:10.1038/s41417-020-00269-2
50 GUO S, HU C, ZHAI X, et al. Circular RNA 0006602 in plasma exosomes: a new potential diagnostic biomarker for hepatocellular carcinoma [J]. Am J Transl Res, 2021, 13(6): 6001-6015.
51 LYU L, YANG W, YAO J, et al. The diagnostic value of plasma exosomal hsa_circ_0070396 for hepatocellular carcinoma [J]. Biomark Med, 2021, 15(5): 359-371. doi:10.2217/bmm-2020-0476
52 LIU L, LIAO R, WU Z, et al. Hepatic stellate cell exosome-derived circWDR25 promotes the progression of hepatocellular carcinoma via the miRNA-4474-3P-ALOX-15 and EMT axes [J]. Biosci Trends, 2022, 16(4): 267-281. doi:10.5582/bst.2022.01281
53 HU Z, CHEN G, ZHAO Y, et al. Exosome-derived circCCAR1 promotes CD8?+?T-cell dysfunction and anti-PD1 resistance in hepatocellular carcinoma [J]. Mol Cancer, 2023, 22(1): 55. doi:10.1186/s12943-023-01759-1
54 YUAN P, SONG J, WANG F, et al. Exosome-transmitted circ_002136 promotes hepatocellular carcinoma progression by miR-19a-3p/RAB1A pathway [J]. BMC Cancer, 2022, 22(1): 1284. doi:10.1186/s12885-022-10367-z
55 HAO X, ZHANG Y, SHI X, et al. CircPAK1 promotes the progression of hepatocellular carcinoma via modulation of YAP nucleus localization by interacting with 14-3-3ζ [J]. J Exp Clin Cancer Res, 2022, 41(1): 281. doi:10.1186/s13046-022-02494-z
56 ZHOU Y, TANG W, ZHUO H, et al. Cancer-associated fibroblast exosomes promote chemoresistance to cisplatin in hepatocellular carcinoma through circZFR targeting signal transducers and activators of transcription (STAT3)/ nuclear factor -kappa B (NF-κB) pathway [J]. Bioengineered, 2022, 13(3): 4786-4797. doi:10.1080/21655979.2022.2032972
57 ZHANG T, SUN Q, SHEN C, et al. Circular RNA circ_0003028 regulates cell development through modulating miR-498/ornithine decarboxylase 1 axis in hepatocellular carcinoma [J]. Anticancer Drugs, 2023, 34(4): 507-518. doi:10.1097/cad.0000000000001457
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