Tumor suppressor and hepatocellular carcinoma

Table 1 Summary of tumor suppressor regulated in HCC

Symbol	Name	Location	Haploinsufficiency	Downregulation in HCC	Mechanism of regulation				Etiology
					Mutation	Methylation	Chromosome change	Protein overcrossing
p53[312–1421232931–33180]	Tumor protein p53	17p13.1	Yes	Yes	√	√			AFB1
									HBV
									HCV
									Cirrhosis
p21[51–53]	Cyclin-dependent kinase inhibitor 1A	6p21.2	Yes	Yes				p53	HBV
									HCV
p27[60]	Cyclin-dependent kinase inhibitor 1B	12p13.1-12p	Yes	Yes		√			cirrhosis
p16[3866–68]	Cyclin-dependent kinase inhibitor 2A	9p21		Yes	√	√			AFB1
p14ARF[38]	Cyclin-dependent kinase inhibitor 2A	9p21		Yes	√	√			HCV
									Cirrhosis
E-cadherin[70–73]	E-cadherin	16q22.1		Yes		√			HBV
									HCV
Axin 1[74–767879]	Axis inhibitor 1	16p13.3		Yes	√		√		HBV
									HCV
Axin 2[757879]	Axis inhibitor 2	17q23-q24		Yes	√		√
APC[81–84]	Adenomatosis polyposis coli	5q21-q22		Yes	√	√	√		HBV
									HCV
SOCS1[8990]	Suppressor of cytokine signaling 1	16p13.13		Yes		√	√		HCV
									Cirrhosis
SOCS3[9394]	Suppressor of cytokine signaling 3	17q25.3		Yes		√
RASSF1A[83104105]	Ras association (ralGDS/AF-6) domain family 1	3p21.3		Yes		√	√		AFB1
									HBV
									HCV
NORE1[94–108]	Ras association (ralGDS/AF-6) domain family 5	1q32.1		Yes		√			HBV
									HCV
									Cirrhosis
KLF6[116119]	Kruppel-like factor 6	10p15		Yes	√	√	√		HBV
									HCV
									Cirrhosis
PTEN[123127128130]	Phosphatase and tensin homolog	10q23.3	Yes	Yes	√			mTOR	AFB1
									HBV
Hint1	Histidine triad nucleotide binding protein	5q31.2	Yes	n.d	n.d	n.d	n.d	n.d
Hint2[144]	Histidine triad nucleotide binding protein 2	9p13.3		Yes	n.d	n.d	n.d	n.d
FHIT[149–151154157]	Fragile histidine triad gene	3p14.2	Yes	Yes		√	√		HBV
									HCV
									Cirrhosis
WWOX[160]	WW domain containing oxidoreductase	16q23.3-q24		Yes			√		AFB1
PARK2[173]	Parkin	6q25.2-q27		Yes