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Table 3 Upstream regulator analysis of the resistant compared to the sensitive cell lines

From: Molecular insight into thiopurine resistance: transcriptomic signature in lymphoblastoid cell lines

Symbol Description Regulator type Predicted activation state P value of overlap (<0.01) Target genes differentially expressed in micro-array
FOXM1 Forkhead box M1 Transcription regulator Inhibited 4.71E-07 ATF2, BIRC5, BUB1B, CCNA2, CCNB1, CDC25A, CDKN3, CENPA, CENPB, FOXM1, GTSE1, MMP2, PLK1
TP53 Tumor protein p53 Transcription regulator Activated 6.41E-05 ACLY, ACTA2, APAF1, ATG10, BIRC5, BTG1, BUB1B, CCNA2, CCNB1, CCNG2, CDC25A, CDC25C, CDKN3, CHUK, CLPP, CYB5A, DDB2, E2F1, EDA2R, EIF4G3, FASN, FBXW7, GNL3, GTSE1, HBEGF, HIF1A, HK2, IPO7, JMJD1C, KIF23, KPNA2, MET, MMP2, NDC80, NPEPPS, NUP153, OAT, ORAI2, PDK1, PIDD, PLK1, PSMD12, PSME3, PVT1, RAD50, RAD54B, RBL2, RFC3, RPS6KB1, SCO2, SFPQ, SGPL1, SLC19A1, SPC25, SQLE, STARD4, TIMM44, TLR6, TMEM97, TRIM28, UBE2C, USO1, USP14, ZFP36L1
FLI1 Fli-1 proto-oncogene, ETS transcription factor Transcription regulator Inhibited 6.18E-04 DDX21, NIP7, NOL6, NOLC1, SNRPB, TCP1
MYC v-myc avian myelocytomatosis viral oncogene homolog Transcription regulator Inhibited 7.33E-04 ASNS, BIRC2, BUB1B, CCNA2, CCNB1, CCNG2, CDC25A, CNBP, DCTPP1, DDB2, DKC1, E2F1, FASN, FOXM1, FTH1, GOT1, GTF2B, HIF1A, HK2, IPO7, ITGA6, MAT2A, NOLC1, OAT, PDK1, PHF21A, PLK1, SHMT2, SLC1A5, SLC3A2, SLC7A5, SNRPD1, SPRR2G, TIMM23, TMEM126A, TXNRD1, UBE2C
CD24 CD24 molecule Other Activated 8.97E-04 CHAC1, DNAJC13, JMJD1C, MBNL1, RAD50, SCAF11, SFPQ, SPG11, USO1, VPS13B, VPS13C
NUPR1 Nuclear protein, transcriptional regulator, 1 Transcription regulator Activated 2.14E-03 BTG1, BUB1B, CCNA2, CDC25C, CDCA2, CDCA8, CHUK, EGLN1, FUT11, GINS1, GPCPD1, GTSE1, HBEGF, HILPDA, HIST1H2AB/HIST1H2AE, HIST1H3A, HK2, KDM3A, KIF23, MAT2A, MTFMT, MTFR2, PDK1, PLK1, RAB7L1, RIMKLA, RNU11, SPC25, UBIAD1, ZFP36L1, ZNF259
CDKN1A Cyclin-dependent kinase inhibitor 1A (p21, Cip1) Kinase Activated 2.36E-03 ACTA2, BIRC5, CCNA2, CCNB1, CDC25A, CDC25C, FOXM1, PLK1, RBL2
CSF2 Colony stimulating factor 2 (granulocyte-macrophage) Cytokine Inhibited 4.34E-03 BIRC5, BUB1B, CCNA2, CDC123, CDCA2, CDCA8, CEACAM1, FOXM1, ITGAX, MAT2A, PLK1, PPIF, SKA1, SLC1A5, SPC25, TRIP13, UBE2C
CCND1 Cyclin D1 Other Inhibited 5.45E-03 BIRC5, BRWD1, CCNA2, CDCA2, CDCA8, CENPN, E2F1, FOXM1, MTFR2, PLK1, SPC25, STARD4, TBCK, TOR3A, TRIP13
  1. Ingenuity® Pathway Analysis was used to determine the most relevant upstream regulators, according to target gene expressions in the micro-array. Changes are expressed in resistant cell lines, using sensitive cell lines as reference.
  2. The P value of overlap was used to rank the significance associated for each upstream regulator. The P value indicates the significance of the overlap between the genes targeted by the upstream regulator in the database and the data from micro-arrays, without taking into account the regulation direction. The activation state makes predictions about potential regulators by using information about the direction of gene regulation and can be used to infer the activation state of a putative regulator. Results with a P value <0.01 are presented in this table.