Background
Results
D6 enters melanoma cells
D6 blocks cell cycle at G2/M transition
D6 treatment induces transcriptional changes in melanoma cells and normal fibroblasts
Cell type | Differentially expressed transcripts | Over-expressed | Under-expressed |
---|---|---|---|
(0.5 > FC > 2) | (FC > 2) | (FC < 0.5) | |
LB 24 DAGI Melanoma cells | 1173 (6.2%) | 681 (3.6%) | 492 (2.6%) |
BJ Fibroblasts | 1883 (10%) | 910 (4.8%) | 973 (5.2%) |
D6 treatment affects cell death and proliferation bio-functions
Bio-Function |
p-value
| N. of molecules |
---|---|---|
1 Cell death | 3.34E-15 – 3.24E-02 | 194 |
2 Cellular function and maintenance | 6.17E-14 – 3.24E-02 | 64 |
3 Cancer | 1.22E-13 – 3.24E-02 | 306 |
4 Cell cycle | 9.64E-12 – 3.15E-02 | 113 |
5 Cellular growth and proliferation | 1.16E-11 – 3.15E-02 | 204 |
D6 induces stress response pathways and down-regulates cell proliferation pathways
Ingenuity canonical pathways | Nominal p-value | Genes |
---|---|---|
1 Aldosterone Signaling in Epithelial Cells | 2.81838E-06 | CRYAB,HSPA7,SGK1,DNAJB4,HSPA1A/HSPA1B,HSPH1,SLC12A2,HSPA6, DNAJC3,HSPD1,DNAJB2,DNAJB9,HSPA5,DNAJA1,DNAJB14,HSPA4,HSPA1L,DUSP1,HSPA13,PIK3R2,DNAJB6,DNAJB1,HSPA4L |
2 Protein Ubiquitination Pathway | 3.98107E-06 | CRYAB,UBE2H,HSPA7,DNAJB4,HSPA1A/HSPA1B,HSPA6,DNAJC3,DNAJB2, HSPA5,DNAJA1,HSPA4,HSPA1L,STUB1,HLA-B, DNAJB1, BRCA1, HSPA4L, MED20, HSPH1, PSMC4, USP30, HSPD1, DNAJB9, DNAJB14, SKP2 (includes EG:27401), ANAPC4, PSMD12, HSPA13, DNAJB6, UBC, UBE2D3 |
3 NRF2-mediated Oxidative Stress Response | 7.58578E-05 | NRAS,DNAJB4,HERPUD1,DNAJC3,DNAJB2,DNAJA1,DNAJB9,DNAJB14,MAFF, TXNRD1, FOS, HMOX1, JUN, ATF4, MAP2K3, FOSL1, PIK3R2, SQSTM1, DNAJB6, DNAJB1, GCLM, EIF2AK3 |
4 Cell Cycle: G2/M DNA Damage Checkpoint Regulation | 0.000177828 | CDC25B, GADD45A, CDKN1A, TOP2A, CCNB2, PKMYT1, BRCA1, SKP2 (includes EG:27401), CCNB1 |
5 p53 Signaling | 0.000194984 | PMAIP1, GADD45B, THBS1, TNFRSF10B, TP53BP2, SERPINE2, SCO2 (includes EG:606683), JUN, GADD45A, CDK4, ADCK3, CDKN1A, PIK3R2, BRCA1 |
6 VDR/RXR Activation | 0.000446684 | GTF2B,LRP5, GADD45A, MXD1, HOXA10, CDKN1A, IGFBP3, CD14, CST6 (includes EG:1474), CSF2, RXRA, KLF4 |
7 Pyrimidine Metabolism | 0.001 | POLE2, DCTPP1, UPP1, POLQ, DKC1, DTYMK, RFC5, POLRMT, PUS1, TXNRD1, POLR1C, POLD3, PNP, POLA2, UNG, ENTPD7 |
8 Mitotic Roles of Polo-Like Kinase | 0.002089296 | CDC25B, PPP2CB, ANAPC4, PLK2, CDC7 (includes EG:12545), CCNB2, PKMYT1, ANAPC13, CCNB1 |
9 IGF-1 Signaling | 0.002818383 | SOCS1, CSNK2A2, FOS, JUN, NRAS, CTGF, NOV, IGFBP3, PRKAG2, IRS2, PIK3R2, CYR61 |
10 Hereditary Breast Cancer Signaling | 0.003467369 | NRAS, GADD45B, FANCG, RFC5, CCNB1, PALB2, GADD45A, CDK4, XPC, CDKN1A, PIK3R2, UBC, BRCA1 |
11 ATM Signaling | 0.003890451 | JUN, GADD45B, GADD45A, CDKN1A, CCNB2, ATF4, BRCA1, CCNB1 |
12 RAR Activation | 0.004265795 | RDH14, BMP2 ,CSK, ADCY3, SMAD5, NFKB1, VEGFA, FOS, CSNK2A2, JUN, TAF4 (includes G:100149942), DUSP1, CRABP2, IGFBP3, PRKAG2, PIK3R2, RXRA |
13 Cyclins and Cell Cycle Regulation | 0.004677351 | PPP2CB, E2F6, TFDP1, CDK4, SUV39H1, CDKN1A, E2F5, CCNB2, SKP2 (includes EG:27401), CCNB1 |
14 p38 MAPK Signaling | 0.005495409 | FADD, DDIT3, DUSP1, DUSP10, MEF2D, H3F3A/H3F3B, ATF4, MAP2K3, MKNK2, EEF2K, H3F3C, IRAK2 |
15 Pancreatic Adenocarcinoma Signaling | 0.005888437 | VEGFA, HMOX1, E2F6, TFDP1, CDK4, SUV39H1, CDKN1A, E2F5, HBEGF, PIK3R2, ERBB2, NFKB1 |
16 Renal Cell Carcinoma Signaling | 0.00691831 | VEGFA,ETS1,FOS,JUN,NRAS,SLC2A1,CRK,PIK3R2,UBC |
17 Cell Cycle Regulation by BTG Family Proteins | 0.00691831 | PPP2CB,E2F6,CDK4,E2F5,BTG1,CCRN4L |
18 Retinoic acid Mediated Apoptosis Signaling | 0.007585776 | FADD,TNKS,CRABP2,TNFRSF10B,TNFRSF10D,RXRA,TIPARP,IRF1 (includes EG:16362) |
19 Glucocorticoid Receptor Signaling | 0.008912509 | IL8,NRAS,HSPA7,SGK1,HSPA1A/HSPA1B,HSPA6,NFKB1,HSPA5,TAF13 (includes EG:310784),FOS,HSPA4,GTF2B,TAF6L,JUN,TAF4 (includes EG:100149942),HSPA1L,DUSP1,CDKN1A,FKBP4,PRKAG2,PIK3R2,CSF2 |
20 Toll-like Receptor Signaling | 0.01023293 | FOS,LY96 (includes EG:17087),JUN,CD14,MAP2K3,NFKB1,IRAK2 |
21 Endoplasmic Reticulum Stress Pathway | 0.010715193 | DNAJC3,ATF4,HSPA5,EIF2AK3 |
22 Neurotrophin/TRK Signaling | 0.013489629 | FOS,JUN,NRAS,SPRY1,ATF4,MAP2K3,PIK3R2,FRS2 |
23 Molecular Mechanisms of Cancer | 0.015488166 | BMP4,SUV39H1,BMP2,CRK,SMAD5,NFKB1,CDC25B,E2F6,JUN,E2F5,PIK3R2, BRCA1,LRP5,PMAIP1,NRAS,STK36,TFDP1,ADCY3,AURKA,FADD,FOS,RND3, CDK4,CDKN1A,PRKAG2,MAP2K3 |
24 Chronic Myeloid Leukemia Signaling | 0.015848932 | E2F6,NRAS,TFDP1,CDK4,SUV39H1,CDKN1A,E2F5,CRK,PIK3R2,NFKB1 |
25 Cell Cycle: G1/S Checkpoint Regulation | 0.016982437 | E2F6,TFDP1,CDK4,SUV39H1,CDKN1A,E2F5,SKP2 (includes EG:27401) |
26 Role of BRCA1 in DNA Damage Response | 0.018620871 | E2F6,GADD45A,FANCG,CDKN1A,E2F5,RFC5,BRCA1 |
27 Role of CHK Proteins in Cell Cycle Checkpoint Control | 0.022387211 | E2F6,CDKN1A,E2F5,RFC5,BRCA1 |
28 Bladder Cancer Signaling | 0.028840315 | VEGFA,IL8,NRAS,TFDP1,THBS1,CDK4,SUV39H1,CDKN1A,ERBB2 |
29 IL-17A Signaling in Gastric Cells | 0.033113112 | IL8,FOS,JUN,NFKB1 |
30 Role of Tissue Factor in Cancer | 0.036307805 | VEGFA,IL8,NRAS,CTGF,ARRB1,PLAUR,HBEGF,PIK3R2,CSF2,CYR61 |
31 HMGB1 Signaling | 0.038904514 | IL8,FOS,JUN,NRAS,RND3,MAP2K3,PIK3R2,NFKB1,KAT2A |
32 ERK/MAPK Signaling | 0.039810717 | ETS1,NRAS,H3F3A/H3F3B,CRK,MKNK2,PPP1R14B,H3F3C,FOS,PPP2CB,ELF3,DUSP1,PRKAG2,ATF4,DUSP4,PIK3R2 |
33 Non-Small Cell Lung Cancer Signaling | 0.041686938 | NRAS,TFDP1,CDK4,SUV39H1,PIK3R2,ERBB2,RXRA |
34 Prostate Cancer Signaling | 0.041686938 | NRAS,TFDP1,SUV39H1,CDKN1A,NKX3-1,ATF4,PIK3R2,NFKB1 |
35 RAN Signaling | 0.042657952 | CSE1L,XPO1,RANBP1 |
36 Cell Cycle Control of Chromosomal Replication | 0.042657952 | MCM3,CDK4,ORC5 (includes EG:26429),CDC7 (includes EG:12545) |
37 IL-6 Signaling | 0.043651583 | IL8,SOCS1,CSNK2A2,FOS,JUN,NRAS,CD14,MAP2K3,NFKB1 |
38 IL-2 Signaling | 0.046773514 | SOCS1,CSNK2A2,FOS,JUN,NRAS,PIK3R2 |
39 MIF Regulation of Innate Immunity | 0.046773514 | FOS,LY96 (includes EG:17087),JUN,CD14,NFKB1 |
40 Role of IL-17F in Allergic Inflammatory Airway Diseases | 0.046773514 | IL8,ATF4,SIK1,CSF2,NFKB1 |
41 Erythropoietin Signaling | 0.047863009 | SOCS1,FOS,PTPN6,JUN,NRAS,PIK3R2,NFKB1 |
42 Estrogen Receptor Signaling | 0.048977882 | TAF6L,GTF2B,NRAS,TAF4 (includes EG:100149942), MED20, H3F3A/H3F3B, MED16,HNRNPD,TAF13 (includes EG:310784),MED10,H3F3C |
GENE | FC | |
---|---|---|
LB | BJ | |
HSPA6
| 368.61 | 480.00 |
HSPA1A
| 20.35 | 12.38 |
CDKN1A
| 19.35 | 4.29 |
DDIT3
| 11.11 | 9.11 |
GADD45A
| 7.78 | 6.00 |
GADD45B
| 7.47 | 14.90 |
PMAIP1
| 6.08 | 7.72 |
BCL10
| 3.93 | 2.02 |
TP53BP2
| 2.36 | – |
CCNF
| 0.24 | – |
KIT
| 0.30 | – |
CDK4
| 0.43 | 0.43 |
CCNB1
| 0.43 | – |
CDC25B
| 0.47 | – |
NFKB1
| 0.47 | – |
PIK3R2
| 0.48 | – |