Introduction
Methods
Drug-Target Search
Network Generation and Pathway Enrichment Analysis
Obtaining Cancer Genomics Data Linked to Pioglitazone Using cBioPortal
Compliance with Ethics Guidelines
Results
Characterization of the Biological Effects of Pioglitazone Using DrugBank and Visualization of the Pioglitazone Linkage Network Using STRING
DB_ID | Name | Group | Category | Indication |
---|---|---|---|---|
DB01132 | Pioglitazone | Approved, Investigational | Blood glucose lowering agents Cytochrome P450 enzyme inducers/inhibitors Peroxisome proliferator-activated receptor alpha/gamma agonists Thiazolidinediones | As an adjunct to diet and exercise to improve glycemic control in adults with T2DM |
DB_ID | Name | Target | UniProt ID | Actions | Organism |
---|---|---|---|---|---|
DB01132 | Pioglitazone | PPARG | P37231 | Agonist | Human |
DB01132 | Pioglitazone | PPARD | Q03181 | Unknown | Human |
DB01132 | Pioglitazone | PPARA | Q07869 | Unknown | Human |
DB01132 | Pioglitazone | MAOB | P27338 | Unknown | Human |
Analysis of Biologic Functions Related to Pioglitazone-Mediated Changes in Genes Using STRING and WebGestalt
Pathway description | #Gene | Genes (corresponding gene set) | FDR |
---|---|---|---|
PPAR signaling pathway | 16 | ACOX1, ADIPOQ, APOA1, APOA5, CD36, CPT1A, CYP7A1, FABP1, FABP4, LPL, PCK1, PLIN1, PPARA, PPARD, PPARG, RXRA | 1.82 × 10−25 |
Adipocytokine signaling pathway | 12 | ADIPOQ, CD36, CPT1A, LEP, NFKB1, NFKBIA, PCK1, PPARA, PPARGC1A, RELA, RXRA, SLC2A4 | 2.38 × 10−17 |
Thyroid hormone signaling pathway | 11 | CREBBP, EP300, HDAC3, MAPK1, MED1, MED24, NCOA1, NCOA2, NCOA3, NCOR1, RXRA | 8.12 × 10−13 |
Pathways in cancer | 13 | CEBPA, CREBBP, EP300, HSP90AA1, MAPK1, NFKB1, NFKBIA, PPARD, PPARG, RB1, RELA, RXRA, TGFB1 | 1.18 × 10−10 |
AMPK signaling pathway | 9 | ADIPOQ, CD36, CPT1A, LEP, PCK1, PPARG, PPARGC1A, SIRT1, SLC2A4 | 1.37 × 10−9 |
Prostate cancer | 8 | CREBBP, EP300, HSP90AA1, MAPK1, NFKB1, NFKBIA, RB1, RELA | 2.70 × 10−9 |
Hepatitis B | 9 | CREBBP, EP300, MAPK1, NFATC1, NFKB1, NFKBIA, RB1, RELA, TGFB1 | 4.00 × 10−9 |
Non-alcoholic fatty liver disease (NAFLD) | 8 | ADIPOQ, CEBPA, LEP, NFKB1, PPARA, RELA, RXRA, TGFB1 | 1.66 × 10−7 |
T cell receptor signaling pathway | 7 | IL2, IL4, MAPK1, NFATC1, NFKB1, NFKBIA, RELA | 2.19 × 10−7 |
Inflammatory bowel disease (IBD) | 6 | IL2, IL4, NFATC1, NFKB1, RELA, TGFB1 | 4.00 × 10−7 |
HTLV-I infection | 9 | CREBBP, EP300, IL2, NFATC1, NFKB1, NFKBIA, RB1, RELA, TGFB1 | 4.52 × 10−7 |
FoxO signaling pathway | 7 | CREBBP, EP300, MAPK1, PCK1, SIRT1, SLC2A4, TGFB1 | 5.40 × 10−7 |
Leishmaniasis | 6 | IL4, MAPK1, NFKB1, NFKBIA, RELA, TGFB1 | 5.40 × 10−7 |
Viral carcinogenesis | 8 | CREBBP, EP300, HDAC3, MAPK1, NFKB1, NFKBIA, RB1, RELA | 5.40 × 10−7 |
Chronic myeloid leukemia | 6 | MAPK1, NFKB1, NFKBIA, RB1, RELA, TGFB1 | 5.40 × 10−7 |
Osteoclast differentiation | 7 | IL2, MAPK1, NFKB1, NFKBIA, RELA, TGFB1 | 6.01 × 10−7 |
Chagas disease (American trypanosomiasis) | 6 | CEBPA, CEBPB, NCOR1, NFKB1, PPARG, RELA, RXRA | 3.32 × 10−6 |
Transcriptional misregulation in cancer | 7 | CEBPB, CREBBP, EP300, MAPK1, NFKB1, RELA, TGFB1 | 3.85 × 10−6 |
Tuberculosis | 7 | HSP90AA1, MAPK1, NFKB1, NFKBIA, RELA | 4.66 × 10−6 |
NOD-like receptor signaling pathway | 5 | ARNTL, CLOCK, CREBBP, EP300, NFKB1, NFKBIA, RELA | 4.77 × 10−6 |
Herpes simplex infection | 7 | CEBPA, MAPK1, NFKB1, PPARD, RELA | 4.77 × 10−6 |
Acute myeloid leukemia | 5 | MAPK1, NFKB1, RB1, RELA, TGFB1 | 4.77 × 10−6 |
Pancreatic cancer | 5 | CREBBP, EP300, NCOR2, NFKB1, NFKBIA, RB1, RELA | 7.03 × 10−6 |
Epstein–Barr virus infection | 7 | MAPK1, NFATC1, NFKB1, NFKBIA, RELA | 7.54 × 10−6 |
B-cell receptor signaling pathway | 5 | IL2, MAPK1, NFKB1, NFKBIA, RELA, TGFB1 | 1.19 × 10−5 |
Pathway name | #Gene | Genes (corresponding gene set) | Statistics |
---|---|---|---|
PPAR signaling pathway | 16 | APOA5, CPT1A, CYP7A1, FABP4, FABP1, APOA1, LPL, ACOX1, PCK1, PLIN1, PPARA, PPARD, PPARG, RXRA, ADIPOQ, CD36 | C = 72, O = 16, E = 0.51 R = 31.26, P = 0 |
Adipocytokine signaling pathway | 12 | PPARGC1A, CPT1A, LEP, NFKB1, NFKBIA, PCK1, PPARA, RELA, RXRA, SLC2A4, ADIPOQ, CD36 | C = 70, O = 12, E = 0.5 R = 24.12, P = 3.26 × 10−14 |
Thyroid hormone signaling pathway | 11 | NCOA2, CREBBP, EP300, MED1, MAPK1, RXRA, NCOA3, NCOA1, HDAC3, NCOR1, MED24 | C = 118, O = 11, E = 0.84 R = 13.11, P = 4.07 × 10−10 |
Th17 cell differentiation | 10 | HSP90AA1, IL2, IL4, NFATC1, NFKB1, NFKBIA, MAPK1, RELA, RXRA, TGFB1 | C = 107, O = 10, E = 0.76 R = 13.15, P = 2.73 × 10−9 |
Insulin resistance | 9 | PPARGC1A, CPT1A, NFKB1, NFKBIA, PCK1, PPARA, RELA, SLC2A4, CD36 | C = 109, O = 9, E = 0.77 R = 11.62, P = 5.52 × 10−8 |
Prostate cancer | 8 | CREBBP, EP300, HSP90AA1, NFKB1, NFKBIA, MAPK1, RB1, RELA | C = 89, O = 8, E = 0.63 R = 12.65, P = 1.68 × 10−7 |
AMPK signaling pathway | 9 | PPARGC1A, CPT1A, SIRT1, LEP, PCK1, PPARG, SLC2A4, ADIPOQ, CD36 | C = 124, O = 9, E = 0.88 R = 10.21, P = 1.70 × 10−7 |
Hepatitis B | 9 | CREBBP, EP300, NFATC1, NFKB1, NFKBIA, MAPK1, RB1, RELA, TGFB1 | C = 146, O = 9, E = 1.04 R = 8.672, P = 6.87 × 10−7 |
Pathways in cancer | 13 | CEBPA, CREBBP, EP300, HSP90AA1, NFKB1, NFKBIA, PPARD, PPARG, MAPK1, RB1, RELA, RXRA, TGFB1 | C = 397, O = 13, E = 2.82 R = 4.607, P = 2.60 × 10−6 |
Th1 and Th2 cell differentiation | 7 | IL2, IL4, NFATC1, NFKB1, NFKBIA, MAPK1, RELA | C = 92, O = 7, E = 0.65 R = 10.7, P = 3.31 × 10−6 |
Inflammatory bowel disease (IBD) | 6 | IL2, IL4, NFATC1, NFKB1, RELA, TGFB1 | C = 65, O = 6, E = 0.46 R = 12.99, P = 5.72 × 10−6 |
Glucagon signaling pathway | 7 | PPARGC1A, CPT1A, CREBBP, EP300, SIRT1, PCK1, PPARA | C = 103, O = 7, E = 0.73 R = 9.561, P = 7.06 × 10−6 |
T-cell receptor signaling pathway | 7 | IL2, IL4, NFATC1, NFKB1, NFKBIA, MAPK1, RELA | C = 105, O = 7, E = 0.75 R = 9.379, P = 8.02 × 10−6 |
cAMP signaling pathway | 9 | CREBBP, EP300, NFATC1, NFKB1, NFKBIA, ACOX1, PPARA, MAPK1, RELA | C = 200, O = 9, E = 1.42 R = 6.331, P = 9.36 × 10−6 |
Non-alcoholic fatty liver disease (NAFLD) | 8 | CEBPA, LEP, NFKB1, PPARA, RELA, RXRA, TGFB1, ADIPOQ | C = 151, O = 8, E = 1.07 R = 7.454, P = 9.45 × 10−6 |
Leishmaniasis | 6 | IL4, NFKB1, NFKBIA, MAPK1, RELA, TGFB1 | C = 73, O = 6, E = 0.52 R = 11.56, P = 1.13 × 10−5 |
Chronic myeloid leukemia | 6 | NFKB1, NFKBIA, MAPK1, RB1, RELA, TGFB1 | C = 73, O = 6, E = 0.52 R = 11.56, P = 1.13 × 10−5 |
Osteoclast differentiation | 7 | NFATC1, NFKB1, NFKBIA, PPARG, MAPK1, RELA, TGFB1 | C = 132, O = 7, E = 0.94 R = 7.461, P = 3.59 × 10−5 |
FoxO signaling pathway | 7 | CREBBP, EP300, SIRT1, PCK1, MAPK1, SLC2A4, TGFB1 | C = 134, O = 7, E = 0.95 R = 7.349, P = 3.95 × 10−5 |
Acute myeloid leukemia | 5 | CEBPA, NFKB1, PPARD, MAPK1, RELA | C = 57, O = 5, E = 0.41 R = 12.34, P = 4.70 × 10−5 |
Longevity-regulating pathway | 6 | PPARGC1A, SIRT1, NFKB1, PPARG, RELA, ADIPOQ | C = 94, O = 6, E = 0.67 R = 8.98, P = 4.82 × 10−5 |
HTLV-I infection | 9 | CREBBP, EP300, IL2, NFATC1, NFKB1, NFKBIA, RB1, RELA, TGFB1 | C = 258, O = 9, E = 1.83 R = 4.908, P = 7.07 × 10−5 |
Chagas disease (American trypanosomiasis) | 6 | IL2, NFKB1, NFKBIA, MAPK1, RELA, TGFB1 | C = 104, O = 6, E = 0.74 R = 8.117, P = 8.52 × 10−5 |
Viral carcinogenesis | 8 | CREBBP, EP300, NFKB1, NFKBIA, MAPK1, RB1, RELA, HDAC3 | C = 205, O = 8, E = 1.46 R = 5.49, P = 8.57 × 10−5 |
Pancreatic cancer | 5 | NFKB1, MAPK1, RB1, RELA, TGFB1 | C = 65, O = 5, E = 0.47 R = 10.66, P = 9.57 × 10−5 |