A Systems’ Biology Approach to Study MicroRNA-Mediated Gene Regulatory Networks

Table 2

The confidence scores for the interactions in p21 regulatory network. The network consists of four types of interactions: miRNA-p21, TF-miRNA, TF-p21, and p21-protein.

(a) miRNA-p21 interaction scores

miRNA	miR-125a-5p	miR-132	miR-208a	miR-28-5p	miR-298	miR-299-5p	miR-345	miR-363
Score	0.73	0.73	0.73	0.80	0.73	0.80	0.73	0.73
miRNA	miR-423-3p	miR-515-3p	miR-572	miR-639	miR-654-3p	miR-657	miR-93
Score	0.85	0.73	0.73	0.73	0.73	0.80	0.95

(b) TF-miRNA interaction scores

	Score		Score		Score		Score		Score		Score
miR-208		miR-132		miR-657		miR-125a-5p		miR-28-5p		miR-93
MAX	0.27	EGR1	0.93	TFAP2A	0.34	EGR1	0.86	MZF1	0.28	TFAP2A	0.34
EGR1	0.29	CREB1	0.86	SP1	0.34	PAX5	0.24	E47	0.27	SOX9	0.24
ARNT	0.27	AREB6	0.27	MZF1	0.34	NRSF	0.24	FOXC1	0.31	GATA3	0.27
RFX1	0.24	E47	0.24	MAX	0.29	ZID	0.24	FOXI1	0.24	MZF1	0.31
ATF6	0.24	ELK1	0.27	USF1	0.27	PPARG	0.27	SRY	0.27	SP1	0.34
YY1	0.27	EGR2	0.29	EGR1	0.34	GATA3	0.34	JUN	0.29	POU2F1	0.24
JUNB	0.24	FOS	0.24	RELA	0.29	MZF1	0.34	POU2F1	0.24	EGR1	0.29
POU2F1	0.24	NFIC	0.24	miR-654-3p		TP53	0.34	SRF	0.27	CEBPA	0.24
NFIC	0.27	RELA	0.27	YY1	0.27	NFIC	0.34	CEBPA	0.29	NFYA	0.24
miR-345		miR-423-3p		BACH1	0.24	miR-299-5p		RORA	0.24	RUNX1	0.24
SP1	0.34	BACH1	0.27	FOXL1	0.29	CREB1	0.24	miR-363		STAT1	0.24
RELA	0.27	STAT1	0.27	SRY	0.24	SRY	0.27	E2F1	0.62	E2F1	0.85
NFATC2	0.24	POU3F2	0.24	NFATC2	0.24	SRF	0.29	FOXC1	0.33	MYC	0.84
HNF4A	0.31	STAT5A	0.27	FOS	0.24	RUNX1	0.27	MZF1	0.34	miR-298
NFYA	0.24	SRF	0.27	POU2F1	0.27	miR-572		miR-639		JUNB	0.31
POU2F1	0.24	MEF2A	0.27	NF𝜅B1	0.24	FOXF2	0.24	NFYA	0.24
NFIC	0.31	POU2F1	0.24	HNF1A	0.24

(c) TF-p21 interaction scores

TF (verified)	SP1	SP3	E2F1	Runx1	Runx2	STAT1	E2A	STAT5	TP53	TP63	TP73
Score	1.00	1.00	0.77	0.77	0.77	0.72	0.72	0.67	0.67	0.67	0.67
TF (verified)	STAT3	CUX1	TFAP2A	BRCA1	VDR	RARA	C/EBPα	C/EBPβ	RB1	Tbx2	EHMT2
Score	0.66	0.66	0.60	0.60	0.60	0.60	0.60	0.60	0.60	0.60	0.60
TF (putative)	NF𝜅B1	RELA	STAT2	STAT6	SRF
Score	0.44	0.44	0.44	0.44	0.43

(d) p21-protein interaction scores

Protein	TP53	PCNA	CASP3	CCNA1	CCND1	SKP2	BCCIP	CCNA2	CCND2	CCNE2	AKT1	C1orf123	CCDC85B	CCNB1	CCNB2	CCND3
Score	1.00	0.92	0.87	0.87	0.87	0.87	0.81	0.81	0.81	0.81	0.72	0.72	0.72	0.72	0.72	0.72
Protein	CCNE1	CDC45	CDC5L	CDC6	CDC7	CDK1	CDK14	CDK2	CDK3	CDK4	CDK6	CEBPA	CIZ1	CSNK2A1	CSNK2B	DAPK3
Score	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72
Protein	ESR1	GADD45A	GADD45B	GADD45G	GMNN	GNB2L1	HDAC11	ITGB1BP3	MAP3K5	MAPK8	MCM10	PARP1	PIM1	POLD2	PSMA3	RAB1A
Score	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72
Protein	SET	SLC25A11	STAT3	TEX11	TK1	TSG101	TTLL5	XRCC6	CDC20	CDC27	CDK5	DHX9	MDM2	NR4A1	PRKCH	RPA1
Score	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.72	0.56	0.56	0.56	0.56	0.56	0.56	0.56	0.56

Verified: experimentally verified interaction; putative: predicted interaction.