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Research advances in exosomal proteins, mRNA and non⁃coding RNA regulation of Hepatocellular Carcinoma
Received date: 2023-11-14
Online published: 2024-04-08
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.
Key words: exosomes; hepatocellular carcinoma; non-coding RNA; diagnosis; prognosis; treatment
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 . DOI: 10.3969/j.issn.1006-5725.2024.06.004
| 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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