Systems analysis reveals a transcriptional reversal of the mesenchymal phenotype induced by SNAIL-inhibitor GN-25

BMC Systems Biology

Table 1 Impact of GN-25 treatment on transcription factor programs in Kras-HMLE-SNAIL cells

Transcription factor	Expression treated/untreated	Predicted activation state	Regulation z-score	p-value of overlap
TBX2	-2.005	Inhibited	-2.978	1.91E-04
MYC	-2.245	Inhibited	-2.912	1.52E-08
NR3C1	-3.751	Inhibited	-2.654	1.21E-08
TWIST1	-4.096	Inhibited	-2.028	3.92E-02
GLI1	2.264	Activated	2.073	3.00E-02
SMAD7	2.005	Activated	2.079	4.17E-06
DDIT3	8.076	Activated	2.110	1.06E-02
CEBPA	4.142	Activated	2.189	9.86E-05
HOXA5	3.132	Activated	2.189	1.27E-01
TFEB	2.098	Activated	2.339	3.92E-02
IRF1	3.651	Activated	2.506	2.84E-02
XBP1	2.026	Activated	3.415	4.11E-01
IRF7	3.915	Activated	3.894	1.32E-04
TP53	NS	Activated	3.502	4.57E-18

Transcription factors whose expression levels (fold-change, treated versus untreated) and predicted activation state are significantly changed by GN-25 treatment in HMLE-SNAIL cells specifically compared to HMLE cells. Although the expression levels of TP53 was not significantly (NS) changed by GN-25 treatment in HMLE-SNAIL cells, its function was predicted to be inhibited in untreated HMLE-SNAIL cells, but activated by GN-25 treatment. Myc-target genes in the data set significantly overlap with a gene set with clinical outcome (dead at 3 years) (Additional file3: Table S2). GN-target genes in the data set overlap significantly with the 3 year clinical outcome metastatic outcomes. Oncomine query matching VV and Koa, respectively.

ISSN: 1752-0509