Table 3.
Tumor suppressor genes upregulated following decitabine treatment for 48 or 72 h in resistant breast cancer (MCF-7/ADR) cells.
| No | Gene Symbol | Entrez Gene I.D | Description | Sub cellular location | Function | Comments |
|---|---|---|---|---|---|---|
| 1 | CD19 | 930 | CD19 molecule | Plasma Membrane | Assembles with antigen receptor of B Lymphocytes | Expression leads to growth inhibition and reduced tumorigenicity in human multiple myeloma29 |
| 2 | CSRP2 | 1466 | Cysteine and glycine rich protein-2 | Nucleus | Development and cell differentiation | Acts as a repressor for NF-kappa B to suppress tumorigenesis and angiogenesis30 |
| 3 | CST6 | 1474 | Cystatin E/M | Extracellular, secreted protein | Physiological inhibitors of lysosomal cysteine proteases | Significantly reduces cell proliferation and migration31,32 |
| 4 | CRMP3 | 10570 | Dihydropyrimidi-nase-like 4 | Cytoplasm | Cell signaling and cytoskeleton remodeling | Direct downstream target of p53 on apoptosis. Apoptosis inducible factor in response to DNA damage33 |
| 5 | DUSP4/MKP2 | 1846 | Dual specificity phosphatase 4 | Nucleus | Negatively regulates Mitogen activated protein (MAP) kinase | Inhibits MAP kinase signaling and thereby cell proliferation. Tumor suppressor in gliomas34 |
| 6 | DUSP5 | 1847 | Dual specificity phosphatase 5 | Nucleus | Negatively regulates Mitogen activated protein (MAP) kinase | Direct transcriptional target of p53 to deactivate MAP - kinase pathway and thereby inhibits cell proliferation35 |
| 7 | ECRG4/C2orf 40 | 84417 | Chromosome 2 open reading frame 40 | Secreted protein | Probable hormone | Putative tumor suppressor gene in various cancers including breast cancer36 |
| 8 | EGR1 | 1958 | Early growth response 1 | Nucleus | Transcriptional regulator | Functions as tumor suppressor via regulation of p53 in skin carcinoma (ref). Direct regulator of multiple tumor suppressors including TGFbeta1, p53, p21 and PTEN37 |
| 9 | HES6 | 55502 | Hairy and enhancer of split 6 | Nucleus | cell differentiation | Inhibits cell proliferation through induction of p2138 |
| 10 | H19 | 283120 | HI9, imprinted maternally expressed transcript (non-protein coding) | Nucleus and Cytoplasm | Acts as translational repressor | Functions as a tumor suppressor in various cancers39 |
| 11 | IBP6 | 3489 | Insulin like growth factor binding protein 6 | Secreted | Binds to IGF-I and -II with high affinity and specificity | Activates programmed cell death in non-small cell lung cancer cells both in vitro and in vivo40 |
| 12 | IF127 | 3429 | Interferon, alpha-inducible protein 27 | Plasma membrane and mitochondria | Promotes cell death | Mediates interferon induced apoptosis characterized by release of cytochrome c, and activation of BAX and caspases - 2,3,6,8 and 9. Also sensitizes cells to other stimulus such as etopside41 |
| 13 | LGALS7 | 3963 | Lectin, galactoside-binding, soluble, 7 | Cytoplasm and nucleus | Involved in cell- cell and/or cell-matrix interactions | Suppresses angiogenesis and tumor growth42 |
| 14 | LXN | 56925 | Latexin | Cytoplasm | Endogenous carboxypeptidase inhibitor | Inhibits lymphoma cell proliferation and proliferation of gastric carcinoma in vitro and in vivo43,44 |
| 15 | MT1F | 4494 | Metallothionein 1F | Cytoplasm and nucleus | Binds various heavy metals | Putative tumor suppressor gene in colon carcinogenesis45 |
| 16 | MT1G | 4495 | Metallothionein 1G | Cytoplasm and nucleus | Binds various heavy metals | Reported as tumor suppressor gene in hepatocellular carcinoma46 |
| 17 | p21 | 1026 | Cyclin-dependent kinase inhibitor 1A | Cytoplasm and nucleus | Binds to and inhibits cyclin-dependent kinase activity | Tumor suppressor, induces cell cycle arrest in cancer cells47 |
| 18 | RASD1 | 51655 | RAS, dexamethasone-induced 1 | Plasma membrane | Regulates cell growth and cell differentiation | Inhibits cell proliferation of G418 resistant MCF 7 breast cancer cells, lung adenocarcinoma A549 and murine fibroblasts (NIH 3T3) cells in vitro48 |
| 19 | SMAD3 | 4088 | SMAD family member 3 | Cytoplasm and nucleus | Signal transducer and transcriptional regulator | In gastric cancer cells, SMAD3 expression restored the expression of TGF-b, p21 and p15, thereby inhibits cancer growth49 |
| 20 | SOCS1 | 8651 | suppressor of cytokine signaling 1 | Intracellular, nucleus | Protein kinase inhibitor, negative regulator of JAK/STAT pathway | Functions as tumor suppressor gene in various cancers including breast carcinomas50–52 |
| 21 | THY1 | 7070 | Thy-1 cell surface antigen | Plasma membrane | Cell- cell adhesion and cytoskeletal organization | Suppresses the growth of human ovarian cancer and nasopharyngeal carcinoma53,54 |