Table 4.
Preclinical targets for the treatment of HCC
| Components | Expression in HCC | Mechanism of action | Functions | First author/s | Year | Ref. |
|---|---|---|---|---|---|---|
| Cell cycle targets | ||||||
| SPAG5 | Up | Related to p53 and cell cycle signal pathway | Indexe of tumor proliferation | Chen W | 2019 | [195] |
| CCT6A | Up | Affect the G1-To-S phase transition | Promote HCC cell proliferation | Zeng G | 2019 | [196] |
| TRIM59 | Up | Degradation of PPM1B | Promote tumor growth in HCC | Ying H | 2019 | [197] |
| CENP-E | Down | Terminate cell cycle at the G1-S phase and accelerate cell apoptosis | Suppress the proliferation of HCC cells | He P | 2019 | [198] |
| DHX9-NONO-SFPQ/BIN1/PLK1 axis | Up | Splicing regulator NONO through oncogenic isoform switch of BIN1 | Enhance carcinogenesis in HCC | Hu Z | 2019 | [199] |
| Apoptosis targets | ||||||
| NQO1 | Up | Inhibit proteasome-mediated degradation SIRT6 | Sustain HCC cell proliferation | Zhou HZ | 2019 | [200] |
| IFITM3-ERK1/2-c-myc path | Up | Upregulate c-myc expression via the ERK1/2 signalling pathway | Promote HCC proliferation | Min J | 2019 | [201] |
| Epigenetic targets | ||||||
| KIAA1429 | Up | m6A-dependent post-transcriptional modification of GATA3 | Contribute to liver cancer progression | Lan T | 2019 | [202] |
| MTF2 | Up | Activate Snail transcription | Induce EMT and progression of HCC | Wu TT | 2019 | [203] |
| miRNAs | ||||||
| miR-1203 | Up | Direct bind and inhibit SOCS3 | Involved in HCC metastases promoted invasion | Shi J | 2019 | [204] |
| miR-16 | Down | Target FEAT through NF-κB signaling pathway | Inhibit HCC progression | Su XF | 2019 | [205] |
| miR-3150b | Down | Target GOLPH3 | Inhibit HCC cell proliferation, migration and invasion | Zhang Y | 2019 | [206] |
| miR-4319 | Down | Target FOXQ1 | Induce an inhibition of EMT and prevented cancer stemness of HCC | Han S | 2019 | [207] |
| miR-541-3p | Down | Directly target and inhibit TMPRSS4 protein expression | Suppress the invasion and migration of HCC cells | Xia YH | 2019 | [208] |
| miR-29a | Down | Via Bcl-2 pathway | Regulate liver tumor-initiating cells expansion | Song S | 2019 | [209] |
| miR-449a | Down | Targeting Notch1 | Inhibit migration and invasion | Han B | 2019 | [210] |
| miR-28-5p | Down | Via IGF-1 Pathway | Regulate liver cancer stem cell expansion | Xia Q | 2019 | [211] |
| miR-181c | Up | Target SPP1 | SPP1 enhances cell growth in HCC | Wang J | 2019 | [212] |
| miR-144 | Down | Target CLK3 | CLK3 contributes to HCC aggressive progression | Li H | 2019 | [213] |
| miR-139 and -378a | Down | Inhibit PIK3CA expression | Inhibitory effects on the proliferation of HCC in vitro | Dong W | 2019 | [214] |
| lncRNAs | ||||||
| GATA3-AS1 | Up | Suppression of PTEN, CDKN1A, and TP53 | Promote cell proliferation and metastasis in HCC | Luo X | 2019 | [219] |
| BZRAP1-AS1 | Up | Mediate THBS1 methylation | Silencing suppresses tumor angiogenesis in HCC | Wang W | 2019 | [217] |
| lncRNA-GMAN | Up | Interact with eIF4B | Promote HCC progression | Xu J | 2019 | [218] |
| RP5-833A20.1 | Down | Through Akt/ERK pathway by targeting miR-18a-5p | Suppress tumorigenesis in HCC | Chen Z | 2019 | [220] |
| AURKAPS1 | Up | Regulate miR-142, miR-155 and miR-182 | Potentiates malignant HCC progression | Li J | 2019 | [221] |
| lncRNA NEAT1 | Up | Regulation of Let-7b-IGF-1R Axis | Promote HCC cell proliferation and reduce apoptosis | Liu Q | 2019 | [222] |
| Regulation of miR-296-5p/CNN2 Axis | Promote proliferation, migration and invasion in HCC cells | Li Y | 2019 | [223] | ||
| ASB16-AS1 | Up | Regulate miR-1827/FZD4 Axis and activate Wnt/β-Catenin Pathway | Promote growth and invasion of HCC | Yao X | 2019 | [224] |
| lncRNA HCG11 | Up | Via miR-26a-5p/ATG12 axis | Accelerate the progression of HCC | Li ML | 2019 | [225] |
| lncRNA TINCR | Up | Sponge miR-214-5p to upregulate ROCK1 | Lead to an increased rate of HCC proliferation | Hu M | 2020 | [226] |
| RP11-81H3.2 | Up | Inhibit microRNA-490-3p and up-regulate Consequential Tankyrase 2 | Act as an oncogene in HCC | Chen W | 2019 | [227] |
| circRNAs | ||||||
| circ_0001955 | Up | Sponge miR-516a-5p to release TRAF6 and MAPK11 | Facilitate HCC tumorigenesis | Yao Z | 2019 | [228] |
| hsa-circ-0046600 | Up | Target the miR-640/HIF-1α signalling pathway | Emerging roles in the progression of HCC | Zhai Z | 2019 | [230] |
| circ_0091579 | Up | Regulate microRNA-490-3p | Promote proliferative ability and metastasis of HCC | Niu WY | 2019 | [231] |
| circ_0003418 | Down | Through Wnt/β-Catenin pathway | Inhibit tumorigenesis in HCC | Chen H | 2019 | [232] |
| circABCB10 | Up | Increase HMG20A expression by sponging miR-670-3p | Promote HCC progression | Fu Y | 2019 | [233] |
| circASAP1 | Up | Regulate miR-326/miR-532-5p-MAPK1 pathway | Promote HCC cell proliferation and invasion | Hu ZQ | 2019 | [229] |
| Metabolic Enzyme/Protease | ||||||
| SOAT1 | Up | Alter the distribution of cellular cholesterol | Promote proliferation and migration of HCC | Jiang Y | 2019 | [234] |
| TGM3 | Up | Depletion inhibiting AKT, ERK, p65 and GSK3β/β-catenin activation | Promote EMT and hepatocellular carcinogenesis | Hu JW | 2019 | [235] |
| OGDHL | Down | Reprogram glutamine metabolism | Silencing promotes HCC | Dai WQ | 2019 | [236] |
| HIF-2α and NEDDylation | Up | SB3 increases HIF-2α stabilization through direct/selective NEDDylation | Favor HCC progression | Cannito S | 2019 | [237] |
| GSTA1 | Down | Regulate LKB1/AMPK/Mtor directly or not | Suppress tumor progression | Liu X | 2020 | [238 |
| Tyrosine kinase pathway targets | ||||||
| Protein Tyrosine Kinase/RTK | ||||||
| SNX5 | Up | Modulate the EGFR-ERK1/2 signaling pathway | Promote HCC progression | Zhou Q | 2019 | [239] |
| HB-EGF | Up | Enhance the expression and proteolytic cleavage by TMPRSS4 | Promote angiogenesis and HCC progression | Dong ZR | 2019 | [240] |
| PlGF | Up | Associated with angiogenesis markers (CD31, CD34, and CD105) | Facilitate neoangiogenesis in HCC | Liu Z | 2019 | [241] |
| MAPK/ERK pathway | ||||||
| p38γ | Up | Promote the phosphorylation of protein at CDK target residues | Induce proliferation after partial hepatectomy | Tomás-Loba A | 2019 | [242] |
| UBE2Z | Up | Target ERK and stat3 signaling pathway | Accelerate HCC progression | Shi X | 2019 | [243] |
| NOD1 | Down | Suppress SRC-MAPK pathway | Inhibit proliferation in HCC | Ma X | 2019 | [244] |
| Immune and inflammatory pathway targets | ||||||
| JAK/STAT pathway | ||||||
| TMUB1 | Down | Regulate Signal Transducer and Activator of Transcription 1 (STAT1) | Negatively regulate HCC proliferation | Chen Y | 2019 | [245 |
| NF-κB signaling pathway | ||||||
| TNFAIP1 | Down | Block NF-κB activation by downregulation of CSNK2B | Tumor suppressor | Xiao Y | 2020 | [246] |
| IGFBP2 | Up | Regulate NF-κB signaling pathway | Promote HCC progression | Guo Q | 2019 | [247] |
| Developmental biology signal transduction targets | ||||||
| OCT4 | Up | Regulate multiple novel HCC signature genes transcription | HCC tumorigenesis and progression | Ye C | 2019 | [248] |
| Wnt/β-catenin pathway | ||||||
| TNKS/β-catenin pathway | Up | Mediate EMT marker expression | An anti-proliferation and anti-metastatic target in HCC cell lines | Huang J | 2020 | [249] |
| UBQLN4 | Up | Activate wnt-β-catenin pathway | Promote progression of HCC | Yu Y | 2020 | [250] |
| MSI1 | Up | Via the Wnt/β-catenin signaling pathway | Increase malignancy of HCC | Liu Q | 2019 | [251] |
| Positively regulate growth and proliferation of hepatoma cells | Li J | 2019 | [252] | |||
| TM4SF1 | Up | Positively regulate β-catenin/TCF signalling | Promote the growth and motility of HCC cells | Zhu C | 2019 | [253] |
| DKK1 | Up | Activate the Wnt/β-catenin signaling pathway | Contribute to HCC tumorigenesis | Zhang R | 2019 | [254] |
| Notch signaling pathway | ||||||
| MSI2 | Up | Via notch1 signaling pathway | Contribute to the maintenance of CD44v6+ liver cancer stem cells | Wang X | 2019 | [255] |
| ZBP-89 | Down | Suppression of Notch1 signaling pathway | Negatively regulate self-renewal of liver cancer stem cells | Wang N | 2020 | [256] |
| Other targets | ||||||
| SEC14L2 | Down | Putative transcriptional activatory activity | Inhibit cancer cells and tumor growth | Li Z | 2019 | [258] |
| Sec62 | Up | Activate integrinα/CAV1 signalling | Promoted migration and invasion of HCC cells | Du J | 2019 | [259] |
| ALOX12-12-HETE-GPR31 axis | Up | 12-HETE upregulated GPR31 and activated PI3K/AKT/NF-κB pathway | Promote recurrence of HCC in fatty liver | Yang F | 2019 | [260] |
HCC (hepatocellular carcinoma), miRNAs (microRNAs), lncRNAs (long non-coding RNAs), circRNAs (circular RNAs).