TABLE 1.

Biologic functions of HCC cell‐derived EVs: Reports from in vitro studies

HCC cell line	EV extraction method	EV molecule expression	Major findings (tumor cells)					Interpretation	References
			Proliferation	Apoptosis	Migration	Chemoresistance	Microenvironment
Hep3B	DC, UF	↑ miR−584‐5p	↑		↑		↑ Angiogenesis	miR−584‐5p increased HCC cell proliferation, migration, and angiogenesis	33
Hep3B, HuH7	DC, Exoquick	↓ circ−0051443	↑	↓ Bak1				HCC cell showed decreased circ−0051443 which acts as a tumor suppressor gene	32
Hep3B, HepG2, PLC/PRF/5	DC, DGC	↑ TUC−339	↑				↓ HCC cell adhesion	TUC−339 increased HCC cell proliferation and might increase invasion/metastasis	34
Hep3B, SNU18, SNU38, Li7, and MHCC97H	DC	↑ ANGPT−2	↑				↑ Angiogenesis	ANGPT−2 increased HCC cell proliferation and angiogenesis	31
MHCC−97L, MHCC−97H	DC, Exoquick	↑ miR−665	↑					miR−665 increased HCC cell proliferation	35
HUH7	DC, UF	↑ miR−122	↓	↑ cleaved PARP, Caspase 9		↓ (Doxorubicin)		HUH7 cell (less‐aggressive cell line) had high miR−122 which decreased HCC cell proliferation, increased apoptosis, and decreased chemoresistance of tumor cell	88
HepG2	UC	↑ linc‐VLDLR	↑			↑ (Sorafenib, Doxorubicin)		linc‐VLDLR increased HCC cell proliferation and chemoresistance	36
HepG2, PLC‐PRF5	DC	↑ linc‐ROR	↑	↓ (Caspase 3/7)		↑ (Sorafenib, Doxorubicin, Camptothecin)		linc‐ROR increased HCC cell proliferation, chemoresistance and decreased HCC cell apoptosis	37
HepG2, HuH7	Ribo exosome isolation reagent	↑lnc 544	↑	↓	↔			Lnc−85, −171, −959, −239, −554 increased HCC cell proliferation Lnc−85, −171, −544 decreased HCC cell apoptosis Lnc−85, −959, −239 increased HCC cell migration	42
		↑lnc 239	↑	↔	↑
		↑lnc 959	↑	↔	↑
		↑lnc 171	↑	↓↓	↔
		↑lnc 85	↑↑	↓↓	↑
97hm, Huhm	UC	↑ miR−92a−3p			↑		↑ Metastasis	miR−92a−3p increased HCC cell migration and metastasis	89
LM3	Exoquick	↑ circ‐PTGR1		↓	↑			High metastatic HCC cell (LM3) had increased EV‐circ‐PTGR1 and was associated with increased cell migration and decreased apoptosis	41

Abbreviations: ABC, ATP‐binding cassette; ANGPT, angiopoietin; circ‐RNA, circular RNA; DC, differential centrifugation; DGC, density‐gradient separation; IGF, insulin growth factor; linc‐ROR, long intergenic noncoding RNA; lnc‐RNA, long noncoding RNA; omiR, oncogenic microRNA; tsmiR, tumor suppressor miRNATUC siRNA, ultraconserved long noncoding siRNA; TUC, tumor ultraconserved RNA; UF, ultrafiltration.