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Page 6 of 12 Jayachandran et al. Hepatoma Res 2018;4:44 I http://dx.doi.org/10.20517/2394-5079.2018.59

Table 2. Preclinical studies demonstrating function of exosomes in HCC
Process HCC cell lines Effect References
mRNA surveillance HepG2, Hep3B Nup98 prevents p21 mRNA degradation by the [52]
exosome
Intercellular communication, Hep3B, HepG2 and PLC/PRF/5 Modulate the constitutive expression and [54]
microRNA-based downstream signalling of TAK1
communication
Long noncoding RNA-based Hep3B and PLC/PRF/5 Transfer of TUC339 to regulate HCC growth [55]
communication
Tumour growth and metastasis SMMC-7721 Self-derived exosomes promote growth and motility [15]
HKCI-C3, HKCI-8, MHCC97L Motile cell-derived exosomes induced motility in non- [56]
and MIHA motile cells
MHCC97-H and SMMC-7721 miR-320a suppresses HCC cell migration [44]
Hep3B cell, 97H and LM3 Motile HCC cells secret more sugar metabolism [28]
regulatory proteins
HepG2 and Hep3B miR-490 rich mast cell-derived exosomes blocked [29]
motility of HCC cells
MHCC97-H and MHCC97-L Enriched adenylyl cyclase associated protein 1 in [57]
motile HCC cells
CSQT-2, HCC-LM3, HepG2 and miR-1247-3p promotes lung metastasis [19]
MHCC-97L
Immune modulation PBTC, MHCC97H, SMCC-7721 14-3-3ζ promotes anti-tumour immune response [32]
DC2.4, Hepa1-6 Induces immune response to suppress tumour growth [4]
Hepa1-6 Induces anti-tumour response by decreasing T [31]
regulatory cells
Chemoresistance HepG2, Hep3B, PLC/PRF-5 and Exposure of HCC cells to diverse anti-cancer agents [59]
Huh-7, MzChA1 cells increased exosomal linc-VLDLR expression
HepG2 and Hep3B miR-122 delivered via exosomes sensitised cells to [49]
doxorubicin and sorafenib
MHCC-97 L, MHCC-97H and Larger tumours formed in mice treated with sorafenib [60]
LO2 and invasive cell-derived exosomes
MHCC97H, MHCC97L, HepG2, Conditioned media from activated fibroblast with high [19]
Huh7, LX2 miR-1247-3p conferred sorafenib resistance
Cancer stem cells HepG2 and PLC/PRF/5 linc-RoR and TGF-β modulated stemness [59]
SMMC-7721 miR-1247-3p enhanced stemness [19]
EMT MHCC97-H Overexpression of miR-320a induces an EMT [44]

the diverse functions of exosomes derived from HCC cells. These functions are summarised in Table 2.
Collectively, these data may provide the foundation for further studies into the regulatory roles of exosomes
in the development and progression of HCC.

mRNA surveillance
Exosomes have been known to participate in control mechanisms that remove aberrant RNAs in the nucleus
and the cytoplasm . In HCC cell lines, HepG2 and Hep3B, the exosomes recognise and degrade p21mRNA
[51]
upon Nup98 depletion as a process of mRNA surveillance related either to impaired export or defects in
RNA protein complex formation in the 3’UTR region .
[52]
Intercellular communication
Exosomes have emerged as important mediators of intercellular communication that can shuttle protein and
RNA to recipient cells and can elicit a potent overall effect on transformed cell tumours [13,53] . For example,
Hep3B, HepG2 and PLC/PRF/5 cell-derived exosomes can modulate the expression of transforming growth
factor-β activated kinase-1(TAK1) and associated downstream signalling and enhance transformed cell
growth in recipient cells . Furthermore, vacuolar protein sortin 4 homolog A (VPS4A) regulates exosome-
[54]
mediated aberrant miRNA expression in HCC cells . The potential of exosomes to transfer lncRNA is
[15]
increasingly recognised. Kogure et al. first demonstrated that lncRNA with highly conserved sequences
[55]
ultraconserved RNAs (ucRNAs) influences intercellular signalling. In HCC cell lines PLC/PRF/5 and Hep3B,
the intercellular transfer of ucRNA TUC339 by exosomes represents a unique signalling mechanism by