TABLE 4.
DCI-INDUCED GENES INHIBITED BY TTF-1 siRNA, BUT NOT INDUCED BY rTTF-1: TTF-1 REQUIRED CANDIDATE GENES
| Gene Title | Gene Symbol | DCI Induction (fold) | siRNA (% Inhibition of DCI Induction) | GO Function |
|---|---|---|---|---|
| Progastricsin (pepsinogen C) | PGC | 111.4 | 52 ± 9 | Proteolysis and peptidolysis |
| Sodium channel, nonvoltage-gated 1 alpha | SCNN1A | 20.1 | 56 ± 30 | Ion transport |
| Claudin 18 | CLDN18 | 16.4 | 66 ± 31 | Cell adhesion |
| Interleukin 1 receptor-like 1 | IL1RL1 | 15.2 | 34 ± 23 | Signal transduction |
| Alcohol dehydrogenase IB (class I), beta polypeptide | ADH1B | 12.1 | 32 ± 2 | Ethanol oxidation |
| Lipoprotein lipase | LPL | 11.1 | 42 ± 2 | Fatty acid metabolism |
| Hypothetical protein FLJ11127 | FLJ11127 | 10.6 | 55 ± 13 | — |
| Melanophilin | MLPH | 7.5 | 44 ± 25 | Intracellular protein transport |
| Sodium channel, nonvoltage-gated 1, beta | SCNN1B | 7.5 | 48 ± 10 | Ion transport |
| Hypothetical protein FLJ21415 | IGF2 | 7.3 | 52 ± 3 | Regulation of cell cycle |
| Aldehyde dehydrogenase 3, B1 | ALDH3B1 | 7.0 | 38 ± 6 | Alcohol metabolism |
| Claudin 5 | CLDN5 | 5.9 | 32 ± 3 | Cell adhesion |
| Nuclear receptor subfamily 4, 2 | NR4A2 | 5.7 | 42 ± 23 | Regulation of transcription |
| BENE protein | BENE | 5.7 | 41 ± 24* | — |
| Pyruvate dehydrogenase kinase, isoenzyme 4 | PDK4 | 5.5 | 52 ± 2 | Glucose metabolism |
| ATPase, aminophospholipid transporter, Class I, type 8A, 1 | ATP8A1 | 5.4 | 46 ± 6 | Cation transport |
| Calcitonin/calcitonin-related polypeptide, alpha | CALCA | 5.4 | 42 ± 12 | Skeletal development |
| Zinc finger and BTB domain containing 16 | ZBTB16 | 4.9 | 48 ± 23 | Regulation of transcription |
| Suppressor of cytokine signaling 3 | SOCS3 | 4.8 | 46 ± 25 | Regulation of cell growth |
| Hypoxia inducible factor 3, alpha subunit | HIF3A | 4.8 | 58 ± 14 | Regulation of transcription |
| Transmembrane protease, serine 2 | TMPRSS2 | 4.8 | 45 ± 3 | Proteolysis and peptidolysis |
| Chloride intracellular channel 5 | CLIC5 | 4.5 | 62 ± 37 | Ion transport |
| Mucin 1, transmembrane | MUC1 | 4.4 | 56 ± 37 | — |
| Hypothetical protein FLJ12443 | FLJ12443 | 4.4 | 44 ± 9 | Metabolism |
| Cytochrome b-5 | CYB5 | 4.4 | 50 ± 30 | Electron transport |
| G protein–coupled receptor kinase 5 | GRK5 | 4.2 | 50 ± 34 | Phosphorylation |
| Intercellular adhesion molecule 4 | ICAM4 | 4.2 | 77 ± 23 | Cell–cell adhesion |
| Solute carrier family 1 (high affinity glutamate transporter), 1 | SLC1A1 | 4.1 | 47 ± 37 | Transport |
| Chromosome 14 open reading frame 147 | C14orf147 | 3.9 | 50 ± 4 | — |
| Fibroblast growth factor receptor 2 (KGF receptor) | FGFR2 | 3.7 | 62 ± 35 | Phosphorylation |
| Interleukin 18 receptor 1 | IL18R1 | 3.6 | 24 ± 4 | Immune response |
| Aldehyde oxidase 1 | AOX1 | 3.5 | 37 ± 17 | Electron transport |
| Fatty acid synthase | FASN | 3.5 | 68 ± 17 | Fatty acid biosynthesis |
| Hypothetical protein MGC11242 | MGC11242 | 3.5 | 58 ± 43 | — |
| Inositol(myo)-1(or 4)-monophosphatase 2 | IMPA2 | 3.4 | 36 ± 20 | Phosphate metabolism |
| Phospholipase D3 | PLD3 | 3.4 | 26 ± 8 | Metabolism |
| Rap guanine nucleotide exchange factor (GEF) 5 | RAPGEF5 | 3.4 | 42 ± 12 | GTPase signal transduction |
| ATP-binding cassette, sub-family C (CFTR/MRP), member 6 | ABCC6 | 3.4 | 75 ± 25 | Transport |
| Phosphodiesterase 4D, cAMP-specific | PDE4D | 3.4 | 34 ± 14* | Signal transduction |
| Growth arrest–specific 1 | GAS1 | 3.2 | 43 ± 8 | Cell cycle arrest |
| KIAA0672 gene product | KIAA0672 | 3.2 | 47 ± 26 | — |
| Estrogen-related receptor beta like 1 | ESRRBL1 | 3.1 | 59 ± 38 | Signaling |
| Platelet/endothelial cell adhesion molecule (CD31 antigen) | PECAM1 | 3.0 | 23 ± 3 | Cell motility |
| Prenylcysteine oxidase 1 | PCYOX1 | 2.9 | 60 ± 16 | Prenylated protein catabolism |
| Serine (or cysteine) proteinase inhibitor, clade A,1 | SERPINA1 | 2.9 | 60 ± 40 | Acute-phase response |
| Hypothetical protein MAC30 | MAC30 | 2.8 | 48 ± 34 | Regulation of cell growth |
| CGI-146 protein | PNAS-4 | 2.8 | 45 ± 35 | — |
| Lanosterol synthase (2,3-oxidosqualene-lanosterol cyclase) | LSS | 2.7 | 64 ± 36 | Steroid biosynthesis |
| Complement component 1, q subcomponent, receptor 1 | C1QR1 | 2.7 | 30 ± 18 | Phagocytosis |
| WAP four-disulfide core domain 2 | WFDC2 | 2.7 | 71 ± 29 | Proteolysis and peptidolysis |
| ATP-binding cassette, sub-family A (ABC1), member 8 | ABCA8 | 2.5 | 19 ± 9 | Signaling, transport |
| Thyroid transcription factor 1 | TITF1 | 2.5 | 59 ± 21* | Regulation of transcription |
| 24-dehydrocholesterol reductase/ | DHCR24 | 2.3 | 42 ± 28* | Electron transport |
| Dihydropyrimidinase-like 2 | DPYSL2 | 2.3 | 45 ± 10 | Nucleic acid metabolism |
| Inhibitor of DNA binding 1 | ID1 | 2.3 | 27 ± 7* | Regulation of transcription |
| ATPase, Na+/K+ transporting, beta 1 polypeptide | ATP1B1 | 2.3 | 20 ± 6 | Transport |
| 7-Dehydrocholesterol reductase | DHCR7 | 2.3 | 49 ± 9 | Cholesterol biosynthesis |
| Chromosome 14 open reading frame 1 | C14orf1 | 2.2 | 64 ± 27 | — |
| Protein tyrosine phosphatase type IVA, member 1 | PTP4A1 | 2.2 | 58 ± 8 | Dephosphorylation |
| Chromosome 9 open reading frame 61 | C9orf61 | 2.2 | 60 ± 40 | — |
| Cyclin D3 | CCND3 | 2.2 | 57 ± 33 | Regulation of cell cycle |
| Deleted in liver cancer 1 | DLC1 | 2.2 | 71 ± 11 | Cytoskeleton organization |
| Flotillin 1 | FLOT1 | 2.1 | 42 ± 20 | — |
| Transmembrane 7 superfamily member 2 | TM7SF2 | 2.1 | 56 ± 43 | Cholesterol biosynthesis |
| ADP-ribosylation factor-like 7 | ARL7 | 2.1 | 53 ± 9 | Intracellular protein transport |
| Diacylglycerol kinase, delta 130 kD | DGKD | 2.1 | 47 ± 7 | Immune response |
| Thiosulfate sulfurtransferase (rhodanese) | TST | 2.0 | 55 ± 23 | Sulfate transport |
| Glucuronidase, beta | GUSB | 2.0 | 74 ± 33 | Carbohydrate metabolism |
| Nuclear receptor co-repressor 2 | NCOR2 | 2.0 | 53 ± 40 | Regulation of transcription |
| RAB27A, member RAS oncogene family | RAB27A | 2.0 | 40 ± 14 | GTPase signal transduction |
| Chromosome 14 open reading frame 132 | C14orf132 | 2.0 | 59 ± 41 | |
| KIAA1280 gene product | KIAA1280 | 2.0 | 34 ± 1 |
For definition of abbreviations, see Table 2.
Cells were treated as in Table 2. Criteria for TTF-1 involvement in the DCI-induction were ⩾ 2-fold induction by DCI, no induction by rTTF-1 alone, and a > 10% inhibition of the DCI induction by TTF-1 siRNA in at least two of three experiments. Seventy-two DCI-induced genes met these criteria, with five genes being inhibited in each of the three experiments.*