TRIM proteins in hepatocellular carcinoma

Lu, Kan; Pan, Yonglong; Huang, Zhao; Liang, Huifang; Ding, Ze-yang; Zhang, Bixiang

doi:10.1186/s12929-022-00854-7

Journal of Biomedical Science

Table 1 Oncogenic/tumor-suppressive role of TRIM proteins in HCC

From: TRIM proteins in hepatocellular carcinoma

Name	Oncogenic or tumor suppressive	Effects	Mechanisms	References
TRIM3	Suppressive	↓ Proliferation ↓ Metastasis	G0/G1 cycle arrest	[87]
TRIM7	Oncogenic	↑ Proliferation	Activate DUSP6/p38 pathway	[43]
	Oncogenic	↑ Proliferation	Inactivate TP53/p21	[43]
	Suppressive	↓ Proliferation ↓ Invasion	Inhibit SRC-mTORC1-S6K1 axis	[14]
	Suppressive	↓ Proliferation ↓ Invasion	Down-regulate SRC	[14]
TRIM10	–	–	Block interaction between IFNAR1 and TYK2	[15]
TRIM11	Oncogenic	↑ Proliferation ↑ Invasion ↑ Metastasis ↓ Autophagy	Down-regulate TP53	[85]
			Promote EMT Activate PI3K/AKT pathway	[103]
			Promote EMT Activate PI3K/AKT pathway	[16]
			Inactivate AMPK pathway	[111]
TRIM16	Suppressive	↓ Invasion ↓ Metastasis	Suppress ZEB2 and EMT	[20]
PML	Oncogenic	↑Arsenic trioxide resistance ↑ Angiogenesis	Up-regulate ALDH3A1	[30]
	Oncogenic	↑Arsenic trioxide resistance ↑ Angiogenesis	Metabolic reprogramming	[113]
	Suppressive	↓ Spontaneous HCC ↑ Apoptosis ↓ Liver steatosis	Strengthen DNA damage response and repair	[126]
			Upregulate TRAIL	[94]
			Suppress IL-6-induced STAT3 activation	[132]
			Transactivate P53	[84, 93]
			Inhibit cancer stem cells	[119]
			Co-activate Fas	[91]
TRIM22	Suppressive	↓ HBV	Inhibit core promoter of HBV	[13, 50]
TRIM23	Oncogenic	↑ Proliferation ↓ Apoptosis	Mediate IKKγ ubiquitination	[51]
TRIM24	Suppressive	↓ Spontaneous HCC ↓ Proliferation ↓ Invasion ↓ Metastasis	Attenuate retinoic acid receptor (RARα)	[117]
			Form regulatory complexes with TRIM28 and TRIM33	[74]
			Chromatin remodeling Inhibit VL30-ERV	[77]
			Inhibit STAT1	[76]
TRIM25	Oncogenic	↑ Proliferation ↓ Apoptosis ↑ Epirubicin resistance	Activate Keap1-Nrf2 pathway	[97]
			Activate PTEN/AKT pathway	[32]
			MAP3K13-TRIM25-FBXW7α-c-Myc protein axis	[88]
	Suppressive	↓ Metastasis ↓ HBV	IFN/IL-27/TRIM25/RIG-1 axis	[124]
	Suppressive	↓ Metastasis ↓ HBV	Down-regulate MTA1	[106, 107]
TRIM26	Oncogenic	↑ HCV	Down-regulate NS5B	[139]
TRIM28	Oncogenic	↑ Warburg effect	Down-regulate FBP1	[110]
	Suppressive	↓ Spontaneous HCC ↑ Sexual dimorphic metabolic syndrome	Epigenetic instability Inactivate AKT pathway Inactivate Wnt/β-catenin pathway	[72]
			ERK1/2-MAPK pathway	[112]
			Chromatin remodeling	[67, 71]
TRIM29	Suppressive	↓ Proliferation ↓ Invasion ↓ Metastasis	Inactivate Wnt/β-catenin pathway	[44]
TRIM31	Oncogenic	↓ Anoikis ↑ Proliferation ↑ Invasion ↓ Autophagy	Down-regulate TSC1–TSC2 to over-activate mTORC1 pathway	[34]
			Over-activate AMPK pathway	[99]
			Down-regulate TP53	[99]
TRIM32	Oncogenic	↑ Proliferation ↑ Oxaliplatin resistance	Accelerate G1 transition	[35]
TRIM33	Oncogenic	↑ Tumor growth (early phase)	Down-regulate SMAD4 to inhibit Smad/TGF-β pathway	[22]
	Suppressive	↓ Spontaneous HCC ↓ Metastasis ↓ Immune escape	Down-regulate SMAD4 to inhibit Smad/TGF-β pathway	[22]
	Suppressive	↓ Spontaneous HCC ↓ Metastasis ↓ Immune escape	circTRIM33-12	[59]
TRIM35	Suppressive	↓ Warburg effect	Inhibit PKM2 phosphorylation	[23, 109]
TRIM37	Oncogenic	↑ Metastasis ↑ Sorafenib resistance	Promote EMT	[36]
			Inactivate β-catenin pathway	[36]
			Activate AKT pathway	[37]
TRIM44	Oncogenic	↑ Proliferation ↓ Apoptosis ↑ Invasion ↑ Migration ↑ Doxorubicin resistance	Accelerate G1/S transition	[38]
			Promote EMT
			Activate NF-κB pathway
			SPATS2/TRIM44/STAT3 axis	[105]
TRIM50	Suppressive	↓ Invasion ↓ Metastasis ↑ Anoikis	Down-regulate SNAIL	[24]
TRIM50	Suppressive	↓ Invasion ↓ Metastasis ↑ Anoikis	Activate Wnt/β-catenin pathway	[24]
TRIM52	Oncogenic	↑ Proliferation ↑ Invasion ↑ Metastasis	Down-regulate PPM1A	[39]
TRIM52	Oncogenic	↑ Proliferation ↑ Invasion ↑ Metastasis	Inactivate TP53	[39]
TRIM55	Suppressive	↓ Invasion ↓ Metastasis	Down-regulate MMP2 to inhibit EMT	[25]
TRIM56	Suppressive	↑ Proliferation	Down-regulate RBM24	[26]
TRIM56	Suppressive	↑ Proliferation	Inactivate Wnt/β-catenin pathway	[26]
TRIM59	Oncogenic	↑ Proliferation ↑ Invasion ↑ Metastasis	Down-regulate PPM1B	[40]
			Accelerate G1/S transition	[40]
			Promote EMT	[86]
TRIM62	Oncogenic	↑ Sorafenib resistance ↑ Proliferation ↑ Invasion	Activate NF-κB pathway	[147]
TRIM65	Oncogenic	↑ Tumor growth ↑ Metastasis	HMGA1/TRIM65/Axin1/β-catenin axis	[83]
TRIM66	Oncogenic	↑ Proliferation ↑ Invasion ↑ Metastasis	Activate Wnt/β-catenin pathway	[101]
TRIM66	Oncogenic	↑ Proliferation ↑ Invasion ↑ Metastasis	Inhibit EMT	[41]
TRIM71	Oncogenic	↑ Proliferation	Inhibit p21 mRNA Non-canonical nonsense-mediated decay	[18]
TRIM71	Oncogenic	↑ Proliferation	Down-regulate AGO2	[42]
TRIM72	Suppressive	↓ Sorafenib resistance	Inhibit RAC1-MAPK pathway	[146]

A summary of functions and specific mechanisms of TRIM proteins in HCC
↑: promoting; ↓: suppressing

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ISSN: 1423-0127

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