Overexpression of ERAP2N in Human Trophoblast Cells Promotes Cell Death
The genes involved in implantation and placentation are tightly regulated to ensure a healthy pregnancy. The endoplasmic reticulum aminopeptidase 2 (ERAP2) gene is associated with preeclampsia (PE). Our studies have determined that an isoform of ERAP2-arginine (N), expressed in trophoblast cells (TC...
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/16/8585 |
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| author | Kristen Lospinoso Mikhail Dozmorov Nadine El Fawal Rhea Raghu Wook-Jin Chae Eun D. Lee |
| author_facet | Kristen Lospinoso Mikhail Dozmorov Nadine El Fawal Rhea Raghu Wook-Jin Chae Eun D. Lee |
| author_sort | Kristen Lospinoso |
| collection | DOAJ |
| description | The genes involved in implantation and placentation are tightly regulated to ensure a healthy pregnancy. The endoplasmic reticulum aminopeptidase 2 (ERAP2) gene is associated with preeclampsia (PE). Our studies have determined that an isoform of ERAP2-arginine (N), expressed in trophoblast cells (TC), significantly activates immune cells, and ERAP2N-expressing TCs are preferentially killed by both cytotoxic T lymphocytes (CTLs) and Natural Killer cells (NKCs). To understand the cause of this phenomenon, we surveyed differentially expressed genes (DEGs) between ERAP2N expressing and non-expressing TCs. Our RNAseq data revealed 581 total DEGs between the two groups. 289 genes were up-regulated, and 292 genes were down-regulated. Interestingly, most of the down-regulated genes of significance were pro-survival genes that play a crucial role in cell survival (LDHA, EGLN1, HLA-C, ITGB5, WNT7A, FN1). However, the down-regulation of these genes in ERAP2N-expressing TCs translates into a propensity for cell death. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that 64 DEGs were significantly enriched in nine pathways, including “Protein processing in endoplasmic reticulum” and “Antigen processing and presentation”, suggesting that the genes may be associated with peptide processes involved in immune recognition during the reproductive cycle. |
| first_indexed | 2024-03-10T08:44:32Z |
| format | Article |
| id | doaj.art-17d830f0d44d49da9ddacd753a4d9628 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:44:32Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-17d830f0d44d49da9ddacd753a4d96282023-11-22T07:57:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216858510.3390/ijms22168585Overexpression of ERAP2N in Human Trophoblast Cells Promotes Cell DeathKristen Lospinoso0Mikhail Dozmorov1Nadine El Fawal2Rhea Raghu3Wook-Jin Chae4Eun D. Lee5Department of Microbiology and Immunology, School of Medicine, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USADepartment of Biostatics and Pathology, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USADepartment of Microbiology and Immunology, School of Medicine, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USATenafly H.S., Tenafly, NJ 07670, USADepartment of Microbiology and Immunology, School of Medicine, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USADepartment of Microbiology and Immunology, School of Medicine, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USAThe genes involved in implantation and placentation are tightly regulated to ensure a healthy pregnancy. The endoplasmic reticulum aminopeptidase 2 (ERAP2) gene is associated with preeclampsia (PE). Our studies have determined that an isoform of ERAP2-arginine (N), expressed in trophoblast cells (TC), significantly activates immune cells, and ERAP2N-expressing TCs are preferentially killed by both cytotoxic T lymphocytes (CTLs) and Natural Killer cells (NKCs). To understand the cause of this phenomenon, we surveyed differentially expressed genes (DEGs) between ERAP2N expressing and non-expressing TCs. Our RNAseq data revealed 581 total DEGs between the two groups. 289 genes were up-regulated, and 292 genes were down-regulated. Interestingly, most of the down-regulated genes of significance were pro-survival genes that play a crucial role in cell survival (LDHA, EGLN1, HLA-C, ITGB5, WNT7A, FN1). However, the down-regulation of these genes in ERAP2N-expressing TCs translates into a propensity for cell death. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that 64 DEGs were significantly enriched in nine pathways, including “Protein processing in endoplasmic reticulum” and “Antigen processing and presentation”, suggesting that the genes may be associated with peptide processes involved in immune recognition during the reproductive cycle.https://www.mdpi.com/1422-0067/22/16/8585ERAP2trophoblast cellspregnancypre-eclampsiaRNA sequencingdifferentially expressed genes |
| spellingShingle | Kristen Lospinoso Mikhail Dozmorov Nadine El Fawal Rhea Raghu Wook-Jin Chae Eun D. Lee Overexpression of ERAP2N in Human Trophoblast Cells Promotes Cell Death International Journal of Molecular Sciences ERAP2 trophoblast cells pregnancy pre-eclampsia RNA sequencing differentially expressed genes |
| title | Overexpression of ERAP2N in Human Trophoblast Cells Promotes Cell Death |
| title_full | Overexpression of ERAP2N in Human Trophoblast Cells Promotes Cell Death |
| title_fullStr | Overexpression of ERAP2N in Human Trophoblast Cells Promotes Cell Death |
| title_full_unstemmed | Overexpression of ERAP2N in Human Trophoblast Cells Promotes Cell Death |
| title_short | Overexpression of ERAP2N in Human Trophoblast Cells Promotes Cell Death |
| title_sort | overexpression of erap2n in human trophoblast cells promotes cell death |
| topic | ERAP2 trophoblast cells pregnancy pre-eclampsia RNA sequencing differentially expressed genes |
| url | https://www.mdpi.com/1422-0067/22/16/8585 |
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