Table 6.
Table of differentially methylated genes related to EMT, and/or metastatic cancers were up-regulated in extravillous trophoblasts compared to cytotrophoblasts.
| Gene | Methylation status at CpGi in promoter region in EVT compared to CTB | Averaged fold change in mRNA expression in EVT compared to CTB | Function/Biological Relevance | Reference |
|---|---|---|---|---|
| ABR | hypomethylated | 2.8* | BCR related protein with functional activity that may regulate Rho family members involved in cytoskeletal reorganisation. | [65] |
| ADAM19 | hypomethylated | 9.1‡ | Involved in the EMT in glioblastoma. | [66] |
| AGRN | hypomethylated | 4.9‡ | AGRN knockdowns reduce oral squamous cell carcinoma migration | [67] |
| AQPEP | hypomethylated | 7.9‡ | An EVT specific protein involved in invasion and migration. | [68] |
| B3GNT7 | hypomethylated | 6.8† | Is upregulated in metastatic breast cancer and enhances cell migration and invasion in vitro. | [69] |
| CAPN2 | hypomethylated | 2.7* | Promotes EMT, migration and invasion in metastatic cancer. | [70] |
| CARD9 | hypomethylated | 4.7* | CARD9 plays a role in manipulating the tumour microenvironment to enhance colon cancer metastasis. | [71] |
| CDR2 | hypomethylated | 3.1† | Upregulated expression of CDR2 is associated with poor prognosis in renal cell carcinoma and may contribute to cancer metastasis. | [72] |
| DLX4 | hypomethylated | 2.5* | Involved in EMT, invasion and migration during embryogenesis and placentation. | [73] |
| FAM163A | hypomethylated | 4.6† | Associated with high-risk neuroblastoma and metastasis to bone marrow. | [74] |
| FERMT3 | hypomethylated | 3.1* | Encourages EMT,invasion, metastasis and angiogenesis in breast cancer. | [75] |
| FLT4 | hypermetylated | 5.8‡ | Associated with metastatic epithelial malignancies and EMT. | [76] |
| HCK | hypomethylated | 3.2* | Contributes to cell migration and actin remodelling. | [77] |
| HMHA1 | hypermethylated | 3.5‡ | Regulates reorganisation of the cytoskeleton and enhancing cell motility | [78] |
| IL17RA | hypomethylated | 2.9† | Involved in gastric cancer migration and osetosarcoma metastasis. | [79] |
| IRF7 | hypomethylated | 2.4† | Enables glioma cell invasion. | [80] |
| KCNF1 | hypomethylated | 2.0† | Ion channel upregulated in invasive cancer. | [81] |
| KIF3C | hypomethylated | 2.7† | Associated with the EMT and breast cancer progression and metastasis. | [82] |
| KLF13 | hypomethylated | 2.1† | Oral cancer cells overexpress KLF13 and contributes to malignancy in other tissues. | [83] |
| KLF6 | hypomethylated | 2.5† | KLF6 is involved in the EMT and present in HER2-ERBB2 positive ductal breast cancer cells. | [84] |
| LHX2 | hypomethylated | 4.4† | Involved in EMT during normal and cancerous breast epithelium development. | [85] |
| LIMS2 | hypomethylated | 3.4* | Involved in interactions which help cell morphology and migration. | [86] |
| LOXL1 | hypomethylated | 7.9‡ | Known to drive EMT in cancers. | [87] |
| LPCAT1 | hypomethylated | 4.3† | Associated with increased breast cancer grade and metastasis. | [88] |
| LRFN4 | hypomethylated | 2.1† | Expressed in both solid tumours and blood cancers. Involved in cytoskeletal reorganisation which allows cell motility. | [89] |
| MICALL2 | hypomethylated | 11.6‡ | Likely an important regulator of EMT in ovarian cancer. Silencing MICALL2 in ovarian cancers inhibits proliferative, invasive and migratory capacity of tumours. | [90] |
| MT1E | hypomethylated | 4.9‡ | Involved in migration and invasion of bladder cancer and glioma. | [91] |
| NCOR2 | hypomethylated | 2.9‡ | Associated with distant metastasis of breast cancer cells | [92] |
| NFATC1 | hypomethylated | 2.8† | Associated with EMT. | [93] |
| NRN1 | hypomethylated | 5.3‡ | Plays a role in the migration of bone marrow derived mesenchymal stem cells. | [94] |
| NUMB | hypermethylated | 3.2† | NUMB isoforms are involved enhancing the EMT and invasion and migration of breast cancer cells. | [95] |
| PIK3CD | hypomethylated | 3.5* | Downregulation of PIK3CD inhibits invasion and migration of colorectal cancer cells | [96] |
| PIM3 | hypomethylated | 2.0† | Overexpression of PIM3 enhances the invasive and migratory capacity of ovarian and prostate cancer cells. Regulates genes that enhance the EMT. | [97] |
| PRDM16 | hypomethylated | 3.3* | Interacts with SKI to enhance gastric cancer growth. | [98] |
| RUSC2 | hypomethylated | 3.7† | Important migration of non-small cell lung cancer. | [99] |
| SKI | hypomethylated | 2.1† | Overexpression in melanoma cells enhances migration in vitro. | [100] |
| SLC16A3 | hypomethylated | 13.7‡ | Associated with hepatocellular carcinoma invasion and migration. Contributes to EMT in breast cancer. | [101] |
| SOD2 | hypomethylated | 3.7* | Mitochondrial enzyme which promotes EMT. | [102] |
| TGFB1 | hypomethylated | 6.6‡ | In later stages of tumorigenesis in vivo TGFB1 promotes the EMT and cancer invasion and metastasis. | [103] |
| TPM2 | hypomethylated | 5.6‡ | Associated with EMT in lens epithelium | [104] |
| WNT1 | hypomethylated | 3.0* | Associated with highly metastatic advanced cancers. Cancer cell migration and invasion can be inhibited though blockade of the Wnt-1 pathway and inhibition of EMT. | [105] |
| ZYX | hypomethylated | 2.8† | Regulates lung cancer cell motility. Involved in reorganisation of cytoskeletal proteins in EMT. | [106] |
Statistically significant values are labelled either *adjusted p value<0.05, † adjusted p value <0.01 or ‡ adjusted p value <0.001. EVT, extravillous trophoblasts; CTB, cytotrophoblast.