Table 2.
Differentially methylated genes and their relationship with MNTI and PAT.
| Gene Name | Gene Function Description | Status MNTI-PAT vs. MBG3 | References |
|---|---|---|---|
| ACOT7 | Lipid metabolism | Hypermethylated | [49] |
| ACSS3 | Lipid metabolism | Hypermethylated | [50] |
| ANO4 | Ca2+ activated Cl- channels | Hypomethylated in PAT Hypermethylated in MNTI | [51] |
| GLT8D2 | GLT8D2 is a glycosyltransferase of apoB100 that regulates apoB100 levels ER | Hypomethylated | [52] |
| HLA-J | Major histocompatibility complex, class I, J (pseudogene) | Hypermethylated | [53] |
| KIAA0040 | HLA-DR11-restricted T-cell epitope encoded by KIAA0040, alcohol dependency | Hypomethylated | [54] |
| LIME1 | Adaptor protein involved in CD4 and CD8 coreceptor signaling | Hypermethylated | [55] |
| OXGR1 | Receptor for alpha-ketoglutarate, expressed in adrenal glands. Frequently hypermethylated in hepatocellular carcinoma | Hypermethylated in PAT, Hypomethylated in MNTI | [56] |
| PCDHGA4 | Neural cadherin-like cell adhesion genes, hypermethylated in neuroblastoma | Hypomethylated | [57,58] |
| RIIAD1 | Regulatory subunit of type II PKA R-subunit domain containing 1 | Hypermethylated | [59] |
| SLC17A8 | GLUT3 (Slc17a8) is expressed in neurons classically defined by their use of another transmitter, such as acetylcholine and serotonin | Hypomethylated | [60] |
| TMEM176B | Innate immune checkpoint | Hypomethylated | [61] |
| TRPC7 | Ca2+ signaling pathway | Hypomethylated | [62] |
| ZNF154 | Candidate Tumor Suppressor ZNF154 suppresses invasion and Metastasis in NPC by inhibiting the EMT via Wnt/β-catenin signaling | hypomethylated in PAT Hypermethylated in MNTI | [63] |
| ACTA1† | α-skeletal actin, WNT target | Hypomethylated in PAT Hypermethylated in MNTI | [64] |
| ALDH3A1† | Target of WNT pathway | Hypermethylated | [65] |
| ASCL2† |
SMYD3 controls a Wnt-responsive epigenetic switch for ASCL2 activation and cancer stem cell maintenance Achaete-scute like 2 (ASCL2) is a target of Wnt signaling and is upregulated in intestinal neoplasia |
Hypermethylated | [64,66,67,68] |
| CCDC8† | Wnt inhibition of CCDC8 phosphorylation or patient-derived mutations | Hypomethylated | [69] |
| ESRP2† | Wnt pathway genes are enriched in genes downregulated by ESRP2 | Hypomethylated | [70] |
| RUNX3† | RUNX3 inhibits glioma survival and invasion via suppression of the β-catenin/TCF-4 signaling pathway | Hypermethylated | [71] |
| ISLR2 * | Essential role of Linx/Islr2 in the development of the forebrain anterior commissure The LRR receptor Islr2 is required for retinal axon routing at the vertebrate optic chiasm |
Hypermethylated in PAT, Hypomethylated in MNTI | [72,73] |
| LYPD1 * | Synaptic signaling | Hypomethylated | [74] |
| NARR/RAB34 * | Genomic characterization of Gli-activator targets in Sonic Hedgehog-mediated neural patterning | Hypermethylated in PAT, Hypomethylated in MNTI | [75] |
| RFX4 * | Zebrafish Rfx4 controls dorsal and ventral midline formation in the neural tube | Hypermethylated in PAT, Hypomethylated in MNTI | [76] |
| SSH2 * | Regulation of actin filaments; neural development and function | Hypomethylated | [77] |
| TUBA1C * | Down-regulation of TUBA1C significantly reduces proliferation and migration in HCC cells Transcriptome analysis of adherens junction pathway-related genes after peripheral nerve injury |
Hypomethylated | [78,79] |
| VRK2 * | VRK2A is an A-type lamin-dependent nuclear envelope kinase that phosphorylates BAF. Associated with schizophrenia and epilepsy | Hypomethylated | [80,81] |
| ALX4 *† |
ALX4, an epigenetically down regulated tumor suppressor, inhibits breast cancer progression by interfering Wnt/β-catenin pathway ALX4 relays sequential FGF signaling to induce lacrimal gland morphogenesis ALX4 and MSX2 play phenotypically similar and additive roles in skull vault differentiation ALX4, a transcriptional activator whose expression is restricted to sites of epithelial-mesenchymal interactions |
Hypermethylated | [82] |
| MEIS1 *† | Cardiac regeneration, stem cells and cancer Meis1 coordinates cerebellar granule cell development by regulating Pax6 transcription, BMP signaling, and Atoh1 degradation. Meis1 is specifically expressed by Sox2(+) stem cells, which give rise to all dental epithelial cell lineages Differential transcriptional regulation of meis1 by Gfi1b and its cofactors LSD1 and CoREST. Potential RA downstream targets play a crucial role in normal development; Combined overexpression of Hoxa9 and Meis1 in hematopoietic stem and progenitor cells (HSPCs) in mice leads to AML and an associated increase in the level of unphosphorylated (“activated”) β-catenin; WNT/β-catenin pathway activation in Myc immortalized cerebellar progenitor cells inhibits neuronal differentiation and generates tumors resembling medulloblastoma (whereas ptf1a, Meis1 and Lhx2 were used as markers of cells in the cerebellar VZ; Meis1 expression was seen in both WNT and Shh groups) |
Hypomethylated | [40] |
| MIR96 *† | Regulates GFI1 MIR-96
is required for normal development of the auditory hindbrain. MIR-96 was identified to indirectly regulate the Wnt/β-catenin pathway by suppressing HMG-box transcription factor protein 1 (HBP-1) |
Hypermethylated | [83] |
* Genes involved in neural function/development. † Genes involved in WNT pathway.