Copyright ©The Author(s) 2022.
World J Hepatol. Dec 27, 2022; 14(12): 1985-1996
Published online Dec 27, 2022. doi: 10.4254/wjh.v14.i12.1985
Table 1 Hepatic cancer stem cell markers and their roles in hepatocellular carcinoma recurrence
Biological functions in LCSCs
Signaling pathways
CD133Tumor angiogenesis, growth, self-renewal, invasion, and chemoresistanceAKT/PKB, IL-8/CXCL1, NotchHigh recurrence[16-23]
CD90Preferably in poorly differentiated HCC, inflammation, circulation, drug resistance, and lipid metabolismTGF-β/SmadA shorter time to recurrence[25-28]
CD44Extensive proliferation, self-renewal, invasion, and tunorigenicityTGF-β, AKT/GSK-3β/β-catenin, AKT/ERK/CXCR4The significant risk factors of recurrence[30-36]
CD24Cell surface glycoprotein, drives CSC genesisStat3/NotchA prognostic predictor for recurrence-free survival[37-41]
CD13Tumorigenicity, cell proliferation, cell cycle, self-renewal, and chemoresistanceERK1/2Early recurrence[42-44]
CD47Tumor initiation, self-renewal, and metastasisCTSS/PAR2, NF-κB, IL-6Shorter recurrence-free survival[45-47]
OV6Invasive and metastatic potential, form tumors, invasiveness, metastasis, substantial chemoresistanceWnt/β-catenin, CXCL12/CXCR4/β-catenin[48,49]
EpCAMAn early biomarker for HCC, self-renewal, differentiation, chemoresistance, highly invasion and tumorigenisisWnt/β-cateninHigh recurrence[50-54]
Table 2 The regulatory roles of miRNAs in hepatocellular carcinoma
Target genes/pathways
Clinical relevance
miR-9-3p HBGF5, lncRNA SAMMSON, ERK1/2 pathwayCell proliferation, migration, and invasionDownLower levels in HCC than in healthy donors[66]
miR-21 KLF5, CAMSAP1, DDX1, MARCKSL1, PTEN, AKT, D24 RECK, PDCD4, TETs/PTENp1/PTEN pathway, TGF-β1/smad3 pathwayCell proliferation, migration, invasion, and metastasisUpHigher in HCC than in CHB and in healthy volunteers, early diagnosis[55-58]
miR-26 ULK1, EphA2, TAK1, TAB3, NF-κB pathwayApoptosisDownPoor survival[67-69]
miR-30a Beclin1, Atg5, Snail1, FOXA1, ADAMTS14, Ras/Raf/MEK/ERK pathwayProliferation, apoptosis, metastasis, migration, invasion, and EMTDownPrevention of HCC recurrence[70-73]
miR-122 ADAM10, ADAM17, IGF1R, SRF, SNAI1, SNAI2, WNT1, CREB1, BCL9, Cyclin G1, NMPDK4, LDHA, and CD133, Wnt/β-catenin pathway, IGF-1R pathwayCell growth, proliferation, differentiation, metabolism, invasion, and EMTDownMore sensitive to chemotherapeutic agents and improves the anti-tumor effect of sorafenib on HCC in vivo[74-78]
miR-125b MCL1, BCLw, IL-6R, SIRT7, SMAD2, SMAD4Proliferation, metastasis, migration, and apoptosisDownA significantly longer time to recurrence and longer overall survival time[79-82]
miR-130b-3pHOXA5UpPoor prognosis, higher in patients with recurrence[59]
miR-142 TGFβ, THBS4, LDHA, CD-133, HMGB1Cell growth, metastasis, migration, and invasionDown[83-85]
miR-155 ZHX2, TP53INP1, TGF-β1 pathwayCell proliferation, migration, invasion, and EMTUpDiagnostic biomarkers for HCC[62, 62]
miR-182-5pFOXO3, AKT, Wnt/β-catenin Proliferation, motility, invasion, and metastasisUpPoor prognosis and early recurrence[63]
miR-199b-5p TGFβ, MAP4K3, DDR1Metastasis, migration, invasion, and EMTDown[86, 87]
miR-200a GAB1, FOXA2Proliferation, invasion, migration, and EMTDownBiomarkers for early-stage HCC[87, 89]
miR-203Ki67, CAPNS1Proliferation, invasion, migration, and metastasisDownTumor recurrence and poor survival of patients with early-stage HCC[90, 91]
miR-221 p53, PUMA, NF-kB, STAT3, AAV8, PTEN, TIMP3, TRAIL, RAS/RAF/ERK, AKTApoptosis, and proliferationUp[64, 65]
miR-449aNotch1, FOS, Met, Calpain6, POU2F1, Notch pathwayMetastasis, apoptosis, proliferation, migration, invasion, and EMTDownShort-term recurrence[92-94]
miR-541ATG2A, RAB1BInhibited the growth, metastasis, and autophagyDownAssociated with malignant clinicopathologic phenotypes, recurrence and survival[95]