实用医学杂志 ›› 2024, Vol. 40 ›› Issue (6): 748-755.doi: 10.3969/j.issn.1006-5725.2024.06.004
收稿日期:
2023-11-14
出版日期:
2024-03-25
发布日期:
2024-04-08
通讯作者:
张萌
E-mail:sygdwkzm@163.com
作者简介:
基金资助:
Yuxin CHENG,Liang LIU,Shiyu DONG,Shengchao LI,Meng ZHANG()
Received:
2023-11-14
Online:
2024-03-25
Published:
2024-04-08
Contact:
Meng ZHANG
E-mail:sygdwkzm@163.com
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。
中图分类号:
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.
Yuxin CHENG,Liang LIU,Shiyu DONG,Shengchao LI,Meng ZHANG. Research advances in exosomal proteins, mRNA and non⁃coding RNA regulation of Hepatocellular Carcinoma[J]. The Journal of Practical Medicine, 2024, 40(6): 748-755.
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
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
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
doi: 10.1126/science.aau6977 |
5 |
SAS Z, CENDROWICZ E, WEINHÄUSER 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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
doi: 10.1097/cad.0000000000001457 |
[1] | 黄秀婷,林颉,叶晓心,蔡佳佐,袁亚维. 铜离子激活MAPK-ERK通路调控鼻咽癌放射敏感性[J]. 实用医学杂志, 2024, 40(9): 1191-1196. |
[2] | 刘景,冷春涛,王艳. circRNA SIPA1L1修饰牙髓干细胞来源外泌体促血管生成能力的机制[J]. 实用医学杂志, 2024, 40(9): 1211-1217. |
[3] | 陈小梅,王安奇,杨积祯,于淼. m1A/m5C/m6A/m7G调控基因预测胃癌预后及免疫关联性[J]. 实用医学杂志, 2024, 40(9): 1230-1237. |
[4] | 黄巧芳,黄杏笑,林俊艺,段炼,庞振泰,伍少娟,邹彩媚,徐世超. 医护-社工联动康复模式对美沙酮维持治疗患者心理状况的影响[J]. 实用医学杂志, 2024, 40(9): 1238-1243. |
[5] | 肖仕和,李钢,刘仲海,刘珍. 脑胶质瘤组织ZEB2、CCL20表达及其与患者预后的相关性[J]. 实用医学杂志, 2024, 40(9): 1262-1267. |
[6] | 崔天玥,欧阳理权,张胜初. 单纯手术与手术联合糖皮质激素治疗肿块型肉芽肿性乳腺炎的临床疗效[J]. 实用医学杂志, 2024, 40(9): 1268-1274. |
[7] | 刘茜,刘晓娜,李超,冼锐,崔立红. 不同方案治疗幽门螺杆菌感染合并小肠细菌过度生长的疗效分析[J]. 实用医学杂志, 2024, 40(9): 1303-1308. |
[8] | 陈甫,刘斌,和帅军,赵勇,王伟周. 男性不育患者精液质量与精浆微量元素水平及精浆外泌体miR-184水平的关系[J]. 实用医学杂志, 2024, 40(7): 930-935. |
[9] | 肖俐,罗淑敏,徐芳,路鹏鹏,邢恩鸿,李伟华. 培养时间对小鼠树突状细胞及其外泌体免疫相关膜蛋白的影响[J]. 实用医学杂志, 2024, 40(7): 941-947. |
[10] | 党富涛,唐映梅,付海艳,李焕龙,徐加敏,谭绪. 非生物型人工肝支持系统治疗原发性胆汁性胆管炎患者的临床疗效及预后影响[J]. 实用医学杂志, 2024, 40(7): 955-961. |
[11] | 马希雅,季虎,朱泽华,潘博,谢强,姚晓波. 根治性放化疗前18F-FDG PET/CT代谢异质性参数结合临床特征对食管鳞状细胞癌预后的预测价值[J]. 实用医学杂志, 2024, 40(7): 966-971. |
[12] | 刘晓童,苏鲜花,辛志军,高奉琼,冯加义,夏同霞. 脊柱结核患者术后并发症危险因素及术前预后营养指数的预测价值[J]. 实用医学杂志, 2024, 40(7): 972-978. |
[13] | 赵敏,倪平,翟惠莹,靳小可,杨玉琼. 淋巴样增强结合因子1在B细胞慢性淋巴增殖性疾病中的表达[J]. 实用医学杂志, 2024, 40(7): 984-988. |
[14] | 李双艳,张斌. 失眠障碍的研究现状与展望[J]. 实用医学杂志, 2024, 40(6): 731-737. |
[15] | 费发珠,芦佳骏,张帅,李浩,任宾. 肝细胞癌免疫及靶向治疗在特殊人群中的临床应用进展[J]. 实用医学杂志, 2024, 40(6): 738-742. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||