Table 1 List of genes known to be modified by the methylation status in renal cell cancer (references in the text)
Gene | Function | Promoter methylation in renal cancer tissue compared to normal tissue | Gene expression in renal cancer tissue compared to normal tissue | Effect of hypomethylating agent on gene expression |
|---|---|---|---|---|
TCF-21 | Tumor suppressor gene involved in specification of differentiation | ↑↑ | ↓ | ↑ |
PCDH17 | Tumor suppressor gene involved in calcium-dependent cell adhesion | ↑↑ | ↓ | ? |
LRRC3B | Tumor suppressor gene involved in cell adhesion and apoptosis | ↑↑ | ↓ | ? |
SFRP1 | Wnt antagonist tumor suppressor | ↑↑↑ | ↓↓ | ? |
RAP1GAP | Tumor suppressor (inactivates Rap-mediated invasion and metastasis) | ↑↑ | ↓ | ↑ |
RASSF1 | Tumor suppressor (cell-cycle control, microtubule stabilization) | ↑↑↑ | ↓↓ | ↑↑ |
UNC5C | Tumor suppressor (induction of apoptosis) | ↑↑ | ↓↓ | ↑↑ |
KILLIN | Tumor suppressor (cell-cycle arrest, regulated by p53) | ↑↑↑ | ↓↓ | ↑↑ |
KRT19 | Organization of myofibrils and maintaining structural integrity of epithelial cells | ↑↑ | ↓↓ | ↑↑ |
HOXA5 | Tumor suppressor (upregulates p53) | ↑ | ? | ? |
MSH-2 | DNA mismatch repair | ↑ | ↓ | ↑ |
miR-9-1 and miR-9-3 | Targeted suppression of gene transcription and translation | ↑ | ↓ | ? |
DKK | Tumor suppressor Wnt direct inhibitor | ↑↑ | ↓ | ↑ (Transfection of gene inhibits cell proliferation and invasion, and increases apoptosis) |
SFRP5 | Tumor suppressor Wnt antagonist | ↑↑↑ | ↓↓ | ↑↑ (Transfection of gene inhibits anchorage independent colony formation ability and invasion and increases apoptosis) |
GATA-3 | TBRIII signaling. inihibitor of cell proliferation | ↑↑↑ | ↓↓ | ↑↑ |
TIMP-3 | VEGF-3 antagonist, matrix metalloproteinase inhibitor | ↑↑ | ↓↓ | ? |
GREM-1 gene | TGF-β signaling inhibition | ↑↑ | ↓↓ | ↑↑ |
WIF-1 | Wnt antagonist | ↑↑↑ | ↓↓ | ↑↑ (Transfection of gene reduced cell viability, suppressed colony formation, and increased apoptosis) |
UCHL1 | Ubiquitination of proteins | ↑↑ | ↓ | ↑ |
BTG3 | E2F1 inhibition → negative regulation of cell cycle | ↑↑↑ | ↓↓ | ↑↑ |
TU3A | Tumor suppressor, mechanism unknown | ↑↑ | ↓ | ↑ |
14-3-3 sigma | Causes G2 phase block for DNA repair | ↑ | ↓ | ↑ |
p16 | Cyclin kinase-dependent inhibition → causes cell-cycle arrest | ↑ | ↓ | ? |
SFRP2 | Wnt antagonist | ↑↑↑ | ↓↓ | ↑↑ |
FHIT | Tumor suppressor, induction of apoptosis | ↑↑ | ↓↓ | ? |
XAF-1 | Pro-apoptotic gene, inhibitor of “inhibition of apoptosis” protein | ↑↑ | ↓ | ↑ |
APAF 1 | Pro-apoptotic gene, activation of caspase 9 | ↑↑↑↑ | ↓↓↓ | ↑↑ |
DAPK-1 | Mediation of IFN-γ induced apoptosis | ↑ | ↓ | ? |
DLC-1 | Inhibitor of RhoAGTPase | ↑ | ↓ | ? |
DLK-1 | Pro-apoptotic gene | ↑↑ | ↓↓ | ↑↑ (Transfection decreases cell proliferation, increases cell apoptosis) |
HOX-B-13 | Pro-apoptotic gene | ↑↑↑ | ↓↓ | ↑↑ (Transfection decreases cell proliferation) |
DAL-1 | Protein 4.1-related tumor suppressor gene | ↑↑ | ↓ | ↑ |
SPINT-2 | Tumor suppressor: inhibits HGF which activates Ras pathway | ↑↑ | ↓ | ? (Transfection decreases cell proliferation) |
Gamma-catenin | Involved in cell-cell adhesion. Loss of function correlates with poorer prognosis in cancer | ↑↑↑ | ↓↓ | ↑↑ |
Connexin-32 | Gap junction protein. May be involved in the increased incidence of RCC in maintenance hemodialysis patients | ↑↑ | ↓↓ | ? |
Ecad | Tumor suppressor: encodes for cell-cell adhesion glycoprotein | ↑↑ | ↓↓ | ↑↑ |
HLA-G | Tumor promoter: involved in helping tumor cells evade immunosurveillance | ? | ↑ | ↑ |
IL-8 | Tumor promoter: promotes angiogenesis and metastasis | ↓ (genomic hypomethylation) | ↑ | ? |
CA9/G250 | Tumor promoter: expressed in hypoxic tumors, produces bicarbonate which neutralizes the surrounding acidic pH and aids cancer progression | ↓↓ | ↑↑ | ↑ |
CYTIP | Promotes metastasis. Helps tumor cells evade cell death cytokines | ↑↑ | ? | ↑ |