Expression and role of nuclear receptor coregulators in colorectal cancer

Table 1 Description of the genes analyzed in the review

Name	Description and aliases	Gene ID	MIM	Location
NCOA1	Nuclear receptor coactivator 1	8648	602691	2p23.3
	F-SRC-1, KAT13A, RIP160, SRC1, bHLHe42, bHLHe74
NCOA2	Nuclear receptor coactivator 2	10499	601993	8q13.3
	GRIP1, KAT13C, NCoA-2, SRC2, TIF2, bHLHe75
NCOA3	Nuclear receptor coactivator 3	8202	601937	20q13.12
	ACTR, AIB-1, AIB1, CAGH16, CTG26, KAT13B, RAC3, SRC-3, SRC3, TNRC14, TNRC16, TRAM-1, bHLHe42, pCIP
NCOA6	Nuclear receptor coactivator 6	23054	605299	20q11.22
	AIB3, ASC2, NRC, PRIP, RAP250, TRBP
PPARGC1A	PPAR gamma, coactivator 1 alpha	10891	604517	4p15.2
	LEM6, PGC-1 (alpha), PGC-1v, PGC1, PGC1A, PPARGC1
EP300	E1A binding protein p300	2033	602700	22q13.2
	histone acetyltransferase p300", KAT3B, p300
CREBBP	CREB-binding protein	1387	600140	16p13.3
	CREBBP, KAT3A, RTS
MED1	Mediator of RNA polymerase II transcription subunit 1	5469	604311	17q12
	TRIP2, MED1, PBP, PPARBP, PPARGBP, CRSP1, CRSP200, DRIP230, RB18A
NCOR1	Nuclear receptor corepressor 1	9611	600849	17p12-p11
	N-CoR, N-CoR1, PPP1R109, TRAC1, hN-CoR
NCOR2	Nuclear receptor corepressor 2	9612	600848	12q24.31
	CTG26, N-CoR2, SMAP270, SMRT, SMRTE, SMRTE-tau, TNRC14, TRAC, TRAC-1, TRAC1
NRIP1	Nuclear receptor interacting protein 1	8204	602490	21q11.2-q21.1
	RIP140
MTA1	Metastasis associated 1	9112	603526	14q32.33

Table 2 Copy number variation and expression levels of nuclear receptor coregulators in human colorectal cancer

Coregulator	CNV (%)	Expression	Ref.
NCOA1	Gain (5.5)	ND
NCOA2	Gain (30.1)	↑ or ↓	Giannini 2005, Grivas 2009, Yu 2016
NCOA3	Gain (40.6)	↑	Anzick 1997, Aust 2004, Xie 2005
NCOA6	Gain (42.7)	↑	Lee 1999
PPARGC1A	Loss (8.4)	↓	D’Errico 2011
EP300	Loss (19.3)	↑	Ishihama 2007
CREBBP	Gain (5.3)	↑	Ishihama 2007
MED1	Gain (11.8) Loss (8.4)	↓	Giannini 2005
NCOR1	Loss (40.4)	↑	Fernández-Majada 2007
NCOR2	Gain (9.8)	↑	Giannini 2005, Fernández-Majada 2007
NRIP1	Loss (17.2)	↓	Lapierre 2014
MTA1	Loss (15.0)	↑	Toh 1997

Gene copy number analysis was performed in 379 CRC samples from the “Carte d’Identité des Tumeurs de la Ligue contre le Cancer” using the Nexus Copy Number software (BioDiscovery, CA, United States). The percentage of CRC specimens showing chromosomic gains and losses are indicated (B. Orsetti, personal communication). Variations in the expression level were determined using the data extracted from the indicated references. ND: Not determined; CRC: Colorectal cancer.

Table 3 Mutations identified in the different nuclear receptor coregulator genes in human colorectal cancer n (%)

Coregulator	216 United States patients (COAD-US)		187 Chinese patients (COCA-CN)
	Patients affected	Mutations	Patients affected	Mutations
NCOA1	6 (2.78)	7	9 (4.81)	14
NCOA2	10 (4.63)	10	26 (13.90)1	32
NCOA3	21 (9.72)1	17	9 (4.81)	10
NCOA6	19 (8.80)1	21	8 (4.28)	10
PPARGC1A	10 (4.63)	12	5 (2.67)	6
EP300	13 (6.02)1	15	14 (7.49)1	21
CREBBP	18 (8.33)1	20	7 (3.74)	11
MED1	3 (1.39)	4	6 (3.21)	6
NCOR1	21 (9.72)1	25	23 (12.30)1	48
NCOR2	41 (18.98)1	43	30 (16.04)1	40
NRIP1	5 (2.31)	5	6 (3.21)	10
MTA1	11 (5.09)1	11	12 (6.42)1	13

Data from the ICGC Data Portal (https://dcc.icgc.org).

¹Indicated genes with mutations detected in more than 5% of patients.

Table 4 Effects of the different nuclear receptors coregulators on the WNT signaling pathway

Coregulator	Effect	Assay	Domains on β-catenin	Ref.
NCoA-1	↑	GPD CoIP	aa 234-585	Li 2004, Tong 2015
NCoA-2	↓	GPD	C-terminal part (aa)	Li 2004, Song 2005, Yu 2016
CREBBP	↑	Y2H GPD CoIP	AR10 to C-ter	Takemaru 2000
N-CoR1		GPD	aa 120-683	Song 2008
N-CoR2		GPD	aa 120-683	Song 2008
NRIP1	↓	CoIP		Zhang 2014

Y2H: Yeast two-hybrid assay; CoIP: Coimmunoprecipitation assay; GPD: GST-pull down assay; AR: Armadillo repeat.