Table 1.
Biological traits possibly affected by 3-MCA treatments, based on the modulated genes over time and related Pathway Maps. Gene modulation (up, ↑; down, ↓; no modulation, —)
| Biological trait / hallmark | Pathway maps | Gene | Up/down regulation | ||||
|---|---|---|---|---|---|---|---|
| 24h | 72h | 32 days | |||||
| 0.04 µg/ml 3-MCA |
4 µg/ml 3-MCA |
0.04 µg/ml 3-MCA |
4 µg/ml 3-MCA |
4 µg/ml 3-MCA |
|||
| Cellular metabolism | Retinol metabolism | Cyp1a1 | ↑ | ↑ | -- | -- | -- |
| Cyp1b1 | ↑ | ↑ | -- | -- | -- | ||
| Xo | ↑ | ↑ | -- | -- | -- | ||
| Estradiol metabolism | Cyp1a1 | -- | -- | ↑ | ↑ | -- | |
| Cyp1b1 | -- | -- | ↑ | ↑ | -- | ||
| Ugt1a10 | -- | -- | ↑ | -- | -- | ||
| Microenvironment / cell adhesion/ cytoskeleton | Cell adhesion_ Chemokines and adhesion |
Acta1 | -- | ↓ | -- | -- | -- |
| Lama4 | ↓ | -- | -- | -- | -- | ||
| Mmp 13 | ↓ | -- | -- | -- | -- | ||
| Cell adhesion_ ECM remodeling |
Lama4 | ↓ | -- | -- | -- | -- | |
| Cytoskeleton remodeling_ RalA regulation pathway |
Arrb1 | -- | ↑ | -- | -- | -- | |
| Acta1 | -- | ↓ | -- | -- | -- | ||
| Neoangiogenesis | Complement pathway disruption in thrombotic micro-angiopathy | C3 | -- | ↑ | ↑ | ↑ | -- |
| Selp | -- | ↑ | -- | -- | -- | ||
|
Ccl5
(Ccl8, Ccl2 Ccl7) |
↓ | ↓ | ↓ | ↑ | ↑ | ||
| Cell death | Apoptosis and survival_ Role of PKR in stress-induced apoptosis | P21 | -- | -- | -- | ↑ | -- |
| Nfkbia | -- | -- | -- | ↑ | -- | ||
| Regulation of GSK3 beta in bipolar disorder |
Irs-1
|
-- | -- | -- | ↓ | -- | |
| Fgfr1 | -- | -- | -- | ↑ | -- | ||
| Nxn | -- | -- | -- | ↓ | -- | ||
| Genomic instability | Development Role of HDAC and calcium/ calmodulin- dependent kinase (CaMK) in control of skeletal myogenesis | P21 | -- | -- | -- | ↑ | -- |
| Hdac5 | -- | -- | -- | ↑ | -- | ||
|
Irs-1
|
-- | -- | -- | ↓ | -- | ||
| Muscle contraction_ Relaxin signaling pathway |
Nfkbia | -- | -- | -- | ↑ | -- | |
| Signal transduction_ AKT signaling | P21 | -- | -- | -- | ↑ | -- | |
| Nfkbia | -- | -- | -- | ↑ | -- | ||
|
Irs-1
|
-- | -- | -- | ↓ | |||
| Immune response | Immune response_Classical complement pathway | C1s2 | -- | ↑ | -- | -- | -- |
| C3 | -- | ↑ | ↑ | ↑ | -- | ||
| Immune response_-Lectin induced complement pathway | C3 | -- | -- | ↑ | ↑ | -- | |
| Immune response_ Alternative complement pathway | C3 | -- | -- | ↑ | ↑ | -- | |
| Ptx3 | ↑ | ↑ | -- | -- | -- | ||
| Immune response_IL-4- responsive genes in type 2 immunity |
Ccl5
(Ccl8, Ccl2 Ccl7) |
-- | -- | ↓ | ↑ | ↑ | |
| Immune response_ Platelet activating factor/ PTAFR pathway signaling |
Arrb1 | -- | ↑ | -- | -- | -- | |
| Nfatc2 | -- | ↓ | -- | -- | -- | ||
| Adcy7 | -- | ↑ | -- | -- | -- | ||
| Nociception_ Expression and role of Nociceptin in immune system |
Ccl5 | ↓ | ↓ | -- | -- | -- | |
| Immune response_IL-4- responsive genes in type 2 immunity | Ccl17 | -- | -- | ↓ | -- | -- | |
| Tff3 | -- | -- | ↓ | -- | -- | ||
| Immune response_TNF-R2 signaling pathways | Traf1 | -- | -- | ↑ | -- | -- | |
| Birc3 | -- | -- | ↑ | -- | -- | ||
| Bmf | -- | -- | ↑ | -- | -- | ||
| Nfkbia | -- | -- | -- | ↑ | -- | ||
| Immune response_MIF- mediated glucocorticoid regulation | Nfkbia | -- | -- | -- | ↑ | -- | |
| Il-6 | -- | -- | -- | -- | ↑ | ||
| Mmp1 | -- | -- | -- | -- | ↑ | ||
| Immune response_Histamine H1 receptor signaling in immune response | Nfkbia | -- | -- | -- | -- | ↑ | |
| Immune response_ IL-4 signaling pathway |
Irs-1
|
-- | -- | -- | ↓ | -- | |
| Immune response_IL-4- induced regulators of cell growth,survival, differentiation and metabolism | Egr2 | -- | -- | -- | -- | ↑ | |
| Mmp13 | -- | -- | -- | -- | ↑ | ||
| Ccne | -- | -- | -- | -- | ↑ | ||
| Immune response_IFN alpha/beta signaling pathway | Stat2 | -- | -- | -- | -- | ↑ | |
| Pmrt1 | -- | -- | -- | -- | ↑ | ||
| Ifn-beta | -- | -- | -- | -- | ↑ | ||
| Usp18 | -- | -- | -- | -- | ↑ | ||
| Isg54 | -- | -- | -- | -- | ↑ | ||
| Immune response_Antigen presentation by MHC class I | Psme2 | -- | -- | -- | -- | ↑ | |
| Psmb8 | -- | -- | -- | -- | ↑ | ||
| Hsp90 | -- | -- | -- | -- | ↑ | ||
|
Tap1,
Tap2 |
-- | -- | -- | -- | ↑ | ||
| Immune response_Oncostatin M signaling via MAPK in human cells | Rac1 | -- | -- | -- | -- | ↑ | |
| Mmp1 | -- | -- | -- | -- | ↑ | ||
| Immune response_Histamine H1 receptor signaling in immune response | Il-6 | -- | -- | -- | -- | ↑ | |
| Mmp1 | -- | -- | -- | -- | ↑ | ||
| Mmp9 | -- | -- | -- | -- | ↓ | ||
| Mmp 13 | -- | -- | -- | -- | ↓ | ||
Full details of the roles of all genes mentioned in this article can be conveniently obtained via the hyperlinks to NCBI Entrez in the Gene Section NCBI Entrez http://www.ncbi.nlm.nih.gov/Entrez/index.html.
As shown, at 32 days, the gene modulation was exclusively ascribable to the highest concentration. At this time point, several sequences associated with tumor progression and metastasis were identified. Table includes genes that have not been discussed in the manuscript. These genes are reported in brackets.