Copyright ©The Author(s) 2023.
World J Gastroenterol. Oct 21, 2023; 29(39): 5435-5451
Published online Oct 21, 2023. doi: 10.3748/wjg.v29.i39.5435
Table 1 Function of exosomal microRNAs from interstitial cells in the liver
miRNA species in exosomesExosome secreting cellsExosome isolation methodsTarget cellsmiRNA expression of exosomeDownstream targetsFunctions of miRNAAdditional informationRef.Year
miR-148a-3pPrimary fibroblasts (the HSC cell line LX-2)The ExoQuick-TC kitHuman HCC cell lines PLC, HCCLM3, and SMMC-7721Reduced in the exosomes of HSCs after cocultivation with primary liver cancer-associated fibroblastsITGA5/PI3K/Akt axisInhibited HCC cell malignancyPrimary fibroblasts were isolated from primary HCC tumor and paired peritumor tissues in 17 primary HCC patient samples[78]2022
miR-335-5pThe HSC cell line LX-2UltracentrifugationHuman HCC cell lines MHCC97H, MHCC97L, HepG2, and Huh7Reduced in the exosomes of fibroblasts as well as in HCC cells after cocultivationCDC42? CDK2?Inhibited neighboring cancer cell proliferation, invasion, and motility-[79]2019
miR-320aCAFsLife Technology exosome precipitation solutionHuman HCC cell lines MHCC97-H, SMMC-7721, Huh7, and the human normal liver cell line 7702Reduced in the exosomes of CAFs derived from human HCC patientsPBX3Inhibited HCC cell proliferation and metastasis abilityPAFs and CAFs derived from 6 pairs of matched primary hepatocarcinoma and adjacent tumor-free tissues (5 cm from the cut edge of the tumor edge)[87]2017
miR-150-3pCAFs0.22-µm PVDF filter and Total Exosome Isolation ReagentHuman HCC cell lines Huh7 and Hep3BDecreased in CAF-derived exosomes-Inhibited HCC proliferation and metastasisStromal fibroblasts isolated from tumor tissue and adjacent (> 5 cm from the tumor edge) tissues from 6 HCC patients[88]2021
miR-20a-5pCAFsCentrifuged and filtered through a 0.22-µm PVDF membraneHuman HCC cell lines SMMC7721, Huh7, YY8103, Hep3B, Focus, HepG2, and HCCLM3 and a normal liver cell line MIHA, WRL68Higher in exosomes from cancer tissues than in matched adjacent para-tumoral tissuesLIMA1Contributed to HCC cell proliferation, metastasis, and EMTCAFs were from the HCC tissues and NFs in paired adjacent normal tissues from 92 HCC patients[89]2022
miR-214hCECsCentrifuged and filtered through a 0.22-µm PVDF membrane and ultracentrifugationHuman HCC cell lines HepG2, Hep3B, the human liver epithelial cell line THLE-2Lower levels in HCC cells than in normal human liver epithelial cellsP-gp/SF3B3Reduced cancer cell viability and invasion compared with monotherapy with oxaliplatin or sorafenib-[103]2021
miR-23a/bAdipose cell mouse preadipocyte 3T3-L1 cellsDifferential centrifugationThe human HCC cell lines BEL-7402 and BEL-7402/5-Fu murine hepatoma cell line Hepa1-6High in exosomes from HCC patients with high BFRVHL/HIF-1αPromoted HCC cell growth and migrationAdipose cells were isolated from human tumor tissues from obese and nonobese patients[95]2019
miR-142, miR-223Monocyte-derived macrophages; human acute monocytic leukemia THP-1, B-lymphoblastoid 721.221, and murine lymphoblast-like mastocytoma P815 cell linesMicrofiltration and ultracentrifugationThe human HCC cell lines Huh7 and HepG2High when cocultured with HCC cellsSTMN-1Inhibited HCC proliferationPBMCs were isolated from lymphocyte cones or fresh blood by density gradient centrifugation and were incubated for 2 h in plastic plates before the flask was washed intensively to remove any nonadherent cells. After 4 d of incubation in serum-free medium supplemented with 1% autologous serum, adherent cells were washed with PBS and cultured in standard DMEM-based medium for 3-6 extra days to generate monocyte-derived macrophages phenotyped to be CD14+, CD11a+, CD3, CD56, and CD19[119]2013
miR-490Human MC line HMC-1 (treated with HCV-E2)Total exosome separation reagent from InvitrogenThe human HCC cell lines HepG2 and HepG3bHigh when HCV-E2-stimulated MC-derived exosomes were incubated with the two types of HCC cells for 24 h compared with the incubation with normal MC-derived exosomesERK1/2Inhibited HCC proliferation[121]2017
miR-223Human NK cell line NK92-MIDifferential centrifugationThe human HSC line LX-2Higher in exosomes derived from NK cells than in parental NK-92MI cellsAGT7Attenuated TGF-β1-induced HSC activation and inhibited liver fibrosisLX-2 cells were treated with TGF-β1 (5 ng/mL) for 24 h to stimulate HSC activation. LX-2 cells in the exosomes derived from NK cells-treated groups were pretreated with exosomes derived from NK cells (10 μg/mL) before TGF-β1 treatment. LX-2 cells in the rapamycin-treated groups were pretreated with the autophagy activator rapamycin (2 mM) in DMSO for 12 h before TGF-β1 treatment[120]2020
miR-125a/bTAMsExoQuick exosome precipitation solutionThe human HCC cell lines Huh7, HepG2, and BEL-7404Downregulated in exosomes from HCC-associated macrophagesCD90Suppressed HCC cell growth and sphere formationTAMs and nontumor macrophages were isolated from primary human HCC, adjacent nontumor liver tissues from 6 patients with HCC[115]2019
miR-628-5pM1 macrophage-The human HCC cell lines Huh7, HCCLM3, Hep3B, and MHCC97H, immortalized human liver epithelial THLE-3 cell lineHigh in M1-exosomesMETTL14/circFUT4/CHMP14BInhibited HCC cell progressionTHP-1 cells were differentiated into M0 macrophages by a 24 h incubation with 150 nM phorbol 12-myristate 13-acetate followed by a 24 h incubation in RPMI medium. M0 macrophages were polarized to M1 macrophages by incubation with 20 ng/mL IFN-γ and 10 pg/mL lipopolysaccharide[118]2022
miR-92a-2-5pM2 macrophage (monocytic leukemia cell line THP-1)Centrifuged and filtered through a 0.22-µm PVDF membrane and ultracentrifugationHuman liver cancer SK-HEP-1 and HepG2 cell lines, HA22T cell line, and murine HCC Hepa 1-6 cell lineIncreased after coculture with liver cancer cellsAR/PHLPP/p-AKT/β-catenin signalingPromoted HCC growth and invasivenessTo induce differentiation into macrophages, THP-1 cells were cultured with 100 ng/mL PMA (Sigma) for 48 h, and the macrophage was cultured with the addition of DMSO to promote M2 polarization[112]2020
miR-660-5pM2 macrophage (monocytic leukemia cell line THP-1)Differential centrifugationHuman HCC cell lines HepG2 and Bel-7402HighKLF3Augmented the tumorigenic ability of HCC cellsTHP-1 monocytes were stimulated by 100 ng of phorbol 12-myristate 13-acetate (Sigma-Aldrich, MO, United States) for 48 h, thus differentiating into M0 macrophages. Then, M0 macrophages were treated with 20 ng/mL interleukin 4 (AF-200–04-5, PeproTech, NJ, United States) for 72 h to polarize into M2 macrophages[114]2021
miR-27a-3pM2 macrophage (monocytic leukemia cell line THP-1)SBI ExoQuick-TC KitHuman HCC cell lines Huh7, 97H, HepG2, LM3, and SMMC-7721-TXNIPInduced the cancer stemness of HCCDifferentiation of THP-1 cells to macrophages was performed using 200 ng/mL phorbol myristic acetate, and the cells were then cultured with 20 ng/mL interleukin-4 for 72 h to induce M2-type polarization[113]2021
miR-142-3pTAMs treated by propofol (the murine macrophage cell line Raw 264.7 cells)Differential centrifugationThe murine HCC cell line Hepa1-6Dose-dependent increase when treated with propofolRAC1Enhanced the antitumor activity of propofolRaw 264.7 cells were cultured in complete RPMI 1640 with 10% FBS and treated with propofol (dissolved in RPMI 1640) in complete medium. TAMs were isolated from tumor-bearing mice treated with 0 mg/kg, 20 mg/kg, and 50 mg/kg propofol by i.p. injection[117]2014
miR-375TAMs (IL-2 induced)Total exosome isolation reagentThe human HCC cell lines HepG2 and QJY–7703High-Ameliorated HCC development and progressionPrimary human HCC specimens were collected from patients who suffered from hepatectomy. The macrophages were isolated and cultured by Percoll (GE Healthcare) density gradient centrifugation. TAMs were treated with IL-2 for 24 h before the supernatants were collected. The treatment concentration was 20 ng/mL[116]2022