Table 1.

Cancers associated with HERCs and related molecular mechanisms.

Genes	Associated Cancers	Related Molecular Mechanisms	Reference
HERC1	Acute promyelocytic leukemia	HERC1-PML genomic fusion	[9]
	Acute Myeloid Leukemia	HERC1 mutations	[10]
	Acute lymphoblastic leukemia	Decreased MSH2 protein levels and HERC1 deletions	[11]
	Adult T-cell acute lymphoblastic leukemia	HERC1 mutations	[12]
	T-cell prolymphocytic leukemia	HERC1 mutations	[13]
	Non-melanoma skin cancer	Enhanced BAK protein degradation	[14]
	Pulmonary sclerosing pneumocytoma	HERC1 mutations	[15]
	Invasive lobular breast cancer	HERC1 mutations	[16]
	Metastatic triple-negative breast cancer	HERC1 mutations	[17]
	Sporadic colorectal cancer	Decreased MSH2 protein levels and HERC1 deletions	[11]
	Osteosarcoma	Negative correlation of SOX18 overexpression and HERC1 mRNA levels	[18]
HERC2	Pheochromocytoma and paraganglioma	HERC2 mutations	[19]
	T-cell prolymphocytic leukemia	HERC2 mutations	[13]
	Cutaneous melanoma	SNPs in HERC2 gene increase susceptibility	[20,21,22,23]
		Gene-gene interactions between HERC2 gene and IL31RA and DDX4 genes	[24]
		Epistatic effects between HERC2 and VDR genes	[25]
	Cutaneous squamous cell carcinoma	SNPs in HERC2 gene impact on time to develop the tumor in organ transplant recipients	[26]
	Uveal melanoma	SNPs in HERC2 gene increase susceptibility	[27]
	Non-small-cell lung cancer	Worse prognosis in patients expressing high HERC2 mRNA levels	[28]
	Breast cancer	Enhanced BRCA1 degradation	[29,30]
	Gastric and colorectal carcinomas	HERC2 mutations	[31]
	Osteosarcoma	Negative correlation of SOX18 overexpression and HERC2 mRNA levels	[18]
HERC3	Glioblastoma	Degradation of SMAD7 and activation of the TGFβ signaling	[32]
	Gastric and colorectal carcinomas	HERC3 mutations	[31]
	Osteosarcoma	Negative correlation of SOX18 overexpression and HERC3 mRNA levels	[18]
HERC4	Multiple myeloma	Decreased c-Maf degradation	[33]
	Lung cancer	HERC4 overexpression	[34]
	Non-small cell lung cancer	Increased Smo protein stability and Hh pathway activation	[35,36]
	Breast cancer	HERC4 upregulation	[37]
		Decreased expression of miRNAs targeting HERC4 expression and enhanced LATS1 degradation	[38]
	Hepatocellular carcinoma	HERC4 overexpression	[39]
	Osteosarcoma	Negative correlation of SOX18 overexpression and HERC4 mRNA levels	[18]
HERC5	Pediatric germ cell tumors	Chromosome copy number variations (CNVs) at a region encompassing HERC5 gene	[40]
	Glioblastoma	HERC5 upregulation	[41]
	Acute myeloid leukemia	HERC5 downregulation	[42]
	Oropharyngeal cancer	HERC5 gene expression is associated with overall survival	[43]
	Non-small cell lung cancer	HERC5 promoter hypermethylation	[44]
	Breast cancer	HERC5 upregulation	[45]
	Hepatocellular carcinoma	Negative correlation of CCL20 overexpression and HERC5 mRNA levels	[46]
		Reduced p53, p21 and Bax/Bcl-2 pathway activation	[47]
	Ovarian cancer	HERC5 upregulation is associated with drug resistance	[48,49]
	Osteosarcoma	Negative correlation of SOX18 overexpression and HERC5 mRNA levels	[18]
HERC6	Osteosarcoma	Negative correlation of SOX18 overexpression and HERC6 mRNA levels	[18]