Table 1.

Functions of SET7/9 and relevant substrates and co-regulators of SET7/9 in different cancer types

Cancer type	Role of SET7/9	SET7/9 expression in clinical sample	Clinical significance	Substrates or interactors	Effects of methylation/ interaction	Biological effects of SET7/9 knockdown
Human breast cancer	Controversial	Overexpression 131	SET7/9 up-regulation is positively correlated with tumor size and grade; Higher SET7/9 expression indicates worse survival 131	VEGF (H3K4) 131	Transcription activation	Decreased cell proliferation, migration, tube formation, tumor growth, and angiogenesis abilities 131
				Estrogen Receptor α (K302) 12	Stabilization of ERα	Attenuated estrogen-driven transcriptional response; Impaired recruitment of ERα to its target genes PS2 and PgR 12
				RUNX2 (H3K4) 143	Transcription activation	Inhibited tumor growth; Inhibited cell migration and invasion 143
		Down-regulation 40	Low SET7/9 expression indicates better overall survival and disease-free survival 40	E2F1 (K185) DNMT1 40	Degradation of E2F1 and DNMT1	Induction of EMT, disruption of cell-cell adhesion and generation of cells with stem cell-like properties 40
Human colorectal cancer	Controversial	Overexpression 145	SET7/9 up-regulation is positively correlated with tumor stage and microsatellite instability 145	E2F1 (K185) 42,145	Stabilization of E2F1	Decreased cell proliferation, migration and invasion 42
				-	-	Decreased cell proliferation; Increased G1/S cell cycle arrest; Increased cell apoptosis 145
		Down-regulation 120, 124	SET7/9 down-regulation is positively correlated with poor prognosis 120, 124	HDAC6 (interaction) 120	Decreased de-acetylation activity of HDAC6	Increased cell proliferation and wound healing rate 120
				RIOK1 (K411) 124	Ubiquitination of RIOK1	Increased cell proliferation, migration, and invasion 124 Enhanced CRC metastasis in vivo
				SIRT1 (K233, K235, K236, K238) 50	Disrupted binding of SIRT1 to p53	Induced p53 deacetylation 50
Human liver cancer	Oncogene	Overexpression 43,144	SET7/9 up-regulation is positively correlated with tumor metastasis, recurrence, large tumor size, and poor tumor differentiation 43,144	E2F1 (K185) 43	Stabilization of E2F1	Decreased cell proliferation, migration and invasion; Decreased expression of E2F1 downstream targets cyclin A2, cyclin E1 and CDK2 43
				ZBTB20 (interaction), CDKN2D (interaction) 144		Increased ZBTB20 and CDKN2D expression; Decreased cell proliferation 144
Human lung cancer	Oncogene	-	-	E2F1(K185) 19,39,41	Degradation of E2F1	Enhanced TP73 expression; Increased cell death; Inhibited cell growth 19,39,41
				Gli3 (K436, K595) 71	Stabilization of Gli3; Increased Gli3-DNA binding capacity.	Suppression of Shh signaling; Inhibited tumor growth and metastasis 71
				Mdm2 (interaction) 44	Increased Mdm2 expression	Defects in DNA repair; Enhanced cell apoptosis; Increased sensitivity to genotoxic stress 44
Mice intestinal tumor	Oncogene	-	SET7/9 up-regulation is positively correlated with tumor susceptibility 90	YAP (interaction) 90	Nuclear accumulation of β-catenin	Decreased expression of Wnt-dependent genes Lgr5, Axin2, and Myc; Diminished Wnt-signaling activation; Fewer intestinal tumors 90
Human gastric cancer	Tumor suppressor	Down-regulation 142	SET7/9 down-regulation is positively correlated with overall survival 142	H3K4 in promoter regions of SREK1IP1, PGC and CCDC28B 142	Enhanced transcription	Increased cell proliferation, migration and invasion; Increased MMPs expression 142
Human glioma	Tumor suppressor	Down-regulation 140	-	H3K4 in the promoter regions of DRAIC 140	Enhanced transcription	Increased cell proliferation, migration and invasion 140
Human osteosarcoma tumor	Tumor suppressor	-	-	pRb (K873) 96	Facilitation of pRb-dependent transcriptional repression 96	Increased expression of E2F target genes E2F1, Cdc6, DHFR, Cdc25A, and Cdc2 downstream of pRb; Reduced cell cycle arrest; Induction of senescent cells 96
				pRb (K810) 97, 98	Hypo-phosphorylation of pRb	Increased DHFR, Cdc2/6, E2F1 expression; Accelerated cell growth 97, 98
				p53 (K372) 18	Stabilization of p53	Inhibited p53 activity; Down-regulation of p21/WAF/CIP and Bax downstream of p53; Defect in cell cycle arrest 18
Human cervical cancer	Tumor Suppressor	-	-	β-catenin (K180) 89	Degradation of β-catenin	Up-regulation of β-catenin and its downstream targets c-myc and cyclin D1; Increased cell proliferation 89
				HIF-1α (K32) 93	Degradation of HIF-1α	Increased cell motility 93
				DNMT1 (K142, K1096) 115,116	Degradation of DNMT1	Reduced cell cycle arrest 115,116

*Letters and numbers in the brackets indicated the methylation site of SET7/9. K, lysine; H3K4, histone H3 lysine 4; interaction, direct interaction detected between SET7/9 and the protein, but no methylation event was reported.