Background
Overview of exosomes
Features of exosomes
Formation and secretion of exosomes
Capture and uptake of exosome
Exosomes and precancerous liver diseases
Viral hepatitis
Alcoholic liver disease
Non-alcoholic fatty liver disease
Hepatocirrhosis
Development of HCC and immunosuppression
Exosomes and the metastasis and progression of HCC
Cargo | Type | Source | Recipient Cell | Function | Mechanism | Ref |
---|---|---|---|---|---|---|
HMGB1 | Protein | HepG2, Huh-7, Hep3B, LM3 | B cell | Promote TIM-1(+) B cell expansion and suppress CD8(+) T cell activity | Activate TLR-MAPK pathway | [16] |
LOXL4 | Protein | SK-Hep1/LOXL4 | SMMC-7721, SK-Hep1 | Promote migration and angiogenesis | Activate FAK/Src pathway to alter cell-matrix adhesion and cell migration ability | [21] |
Melatonin | Protein | HepG2, Bel7402 | Macrophage | Reverse immunosupression | Suppress p-STAT3 and decrease PD-L1 expression | [129] |
Vasorin | Protein | HepG2 | HUVEC | Promote proliferation and migration | Not mention | [160] |
GOLM1 | Protein | MHCC97H | MHCC97H | Promote proliferation, migration and invasion | Activate GSK-3β/MMPs axis | [161] |
SMAD3 | Protein + RNA | Huh-7 | Huh-7 | Promote proliferation and adhesion | Enhance TGF-β-SMAD3-ROS signal | [147] |
circ-DB | RNA | 3T3L1 | HepG2 | Promote tumor growth and inhibit DNA damage | Suppress miR-34a expression and enhance USP7 and Cyclin A2 expression | [15] |
circ-PTGR1 | RNA | LM3 | HepG2, 97L | Promote migration, invasion and metastasis | Activate MET via interacting with miR-449a | [202] |
linc-ROR | RNA | HepG2 | HepG2 | Tolerance to hypoxia | Neutralize miR-145 and upregulate HIF-1α | [142] |
linc-ROR | RNA | HepG2 | HepG2 | Induce chemoresistance | Not mention | [211] |
linc-VLDLR | RNA | HepG2 | HepG2, KMBC | Promote chemoresistance | Increase expression of ABC-G2 and ABC-C1 | [212] |
lncRNA-H19 | RNA | Huh-7 (CD90+) | HUVEC | Promote tube formation and cell-cell adhesion | Increase VEGF and ICAM1 | [146] |
lncRNA-FAL1 | RNA | HCC patients serum | Huh-7, HepG2 | Promote proliferation and migration | Suppress miR-1236 and upregulate ZEB1 and AFP | [152] |
miR-21 | RNA | MHCC97H | LX2 | Convert normal HSCs to cancer-associated fibroblasts | Depress PTEN, upregulate PDK1/AKT pathway and promote lipogenesis | [14] |
miR-1247-3p | RNA | CSQT-2, LM3 | Fibroblast | Promote tumorstemness, EMT, chemoresistance, tumorigenicity and metastasis | Downregulate B4GALT3 and activate β1-integrin/NF-κB axis | [134] |
miR-125a/b | RNA | TAM | Huh-7, HepG2 | Suppress proliferation, stem cell properties and migration | Decrease CD90 expression | [137] |
miR-210 | RNA | QGY-7703 | HUVEC | Promote tubulogenesis | Inhibit SMAD4 and STAT6 | [143] |
miR-155 | RNA | Huh-7, PLC/PRF/5 | HUVEC | Promote tube formation under hypoxia condition | Not mention | [145] |
miR-103 | RNA | QGY-7703 | HUVEC | Increase permeability of endothelial monolayers and facilitate transendothelial invasion | Decrease VE-Cad, p120 and ZO-1 to attenuate endothelial adhesion junction integrity | [148] |
miR-32-5p | RNA | Bel7402/5-FU | Bel7402 | Induce multidrug resistance via angiogenesis and EMT | Suppress PTEN and activate PI3K/Akt pathway | [149] |
miR-25-5p | RNA | Huh-7, LM3 | Huh-7, LM3 | Stimulate transendothelial motility and enhance CTC tumor self-seeding ability | Inhibit LRRC7 expression | [150] |
miR-93 | RNA | HCC patients serum | SK-Hep1, Huh-7 | Stimulate proliferation and invasion | Suppress CDKN1A, TP53INP1 and TIMP2 | [151] |
miR-122 | RNA | AMSC | HepG2 | Induce chemosensitivity and cell cycle arrest | Downregulate Cyclin G1, ADAM10 and IGF1R | [222] |
miR-320a | RNA | CAF | MHCC97H, SMMC-7721 | Inhibit proliferation and metastasis ability | Suppress PBX3/ERK1/2/CDK2 axis | [225] |
Exosomes and HCC diagnosis
Factors as biomarker | Potential Mechanism | Exosome isolation methods | Ref |
---|---|---|---|
circ-0008043, circ-0003731, circ-0088030↑ | Promote migration, invasion and metastasis | Exoquick (System Biosciences, USA) | [202] |
LINC00161↑ | Promote tumor migration and invasion | Total exosome isolation kit (Invitrogen, USA) | [196] |
LINC-000635, ENSG00000258332.1↑ | Positive related to portal vein tumor emboli, lymph node metastasis and worse OS | Total exosome isolation reagent (Thermo Fisher Scientific Co. Ltd, USA) | [199] |
lncRNA-FAL1↑ | Promote proliferation and migration | Exoquick TC (System Biosciences, USA) | [152] |
lncRNA-HEIH↑ | Promote tumor progression | GS0301 (Guangzhou Geneseed Biotech Co, China) | [198] |
lncRNA-RP11-513I15.6, mRNA-RAB11A↑, miR-1262↓ | Associate with poor prognosis | ExoRNeasy® RNA isolation kit (Qiagen, USA) | [201] |
miR-21↑ | Correlate with tumor stage | Total exosome isolation reagent (From serum) (Invitrogen, USA) | [17] |
miR-21↑, lncRNA-ATB↑ | Short progression time and OS | Exoquick (System Biosciences, USA) | [19] |
miR-155↑ | Promote tube formation under hypoxia condition | Exoquick (System Biosciences, USA) | [145] |
miR-93↑ | Stimulate proliferation and invasion | Total exosome isolation reagent (Thermo Fisher Scientific Co. Ltd, USA) | [151] |
miR-638↓ | Inhibit cancer cells proliferation | Total exosome isolation kit (Invitrogen, USA) | [174] |
miR-9-3p↓ | Suppress proliferation | Ultracentrifugation | [176] |
miR-92b↑ | Promote migration and affect NK cell cytotoxicity via downregulating CD69 | Exoquick (System Biosciences, USA) | [181] |
miR-718↓ | Suppresses cell proliferation via targeting HOXB8 | Ultracentrifugation | [182] |
miR-125b↓ | Short TTR and OS | Exoquick (System Biosciences, USA) | [194] |
mRNA-hnRNPH1↑ | Positive related to poor differentiation and worse OS | Total exosome isolation reagent (Thermo Fisher Scientific Co. Ltd, USA) | [175] |
G3BP↑, PIGR↑ | Promote tumor progression, transformation, invasion and proliferation | Ultracentrifugation | [206] |