{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T12:22:36Z","timestamp":1772799756445,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009238","name":"Virginia Commonwealth University","doi-asserted-by":"publisher","award":["Center for Clinical and Translational Research (CCTR) Pilot Grant"],"award-info":[{"award-number":["Center for Clinical and Translational Research (CCTR) Pilot Grant"]}],"id":[{"id":"10.13039\/100009238","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u201cProtein processing in endoplasmic reticulum\u201d and \u201cAntigen processing and presentation\u201d, suggesting that the genes may be associated with peptide processes involved in immune recognition during the reproductive cycle.<\/jats:p>","DOI":"10.3390\/ijms22168585","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T08:57:14Z","timestamp":1628585834000},"page":"8585","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Overexpression of ERAP2N in Human Trophoblast Cells Promotes Cell Death"],"prefix":"10.3390","volume":"22","author":[{"given":"Kristen","family":"Lospinoso","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0086-8358","authenticated-orcid":false,"given":"Mikhail","family":"Dozmorov","sequence":"additional","affiliation":[{"name":"Department of Biostatics and Pathology, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine","family":"El Fawal","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0491-3400","authenticated-orcid":false,"given":"Rhea","family":"Raghu","sequence":"additional","affiliation":[{"name":"Tenafly H.S., Tenafly, NJ 07670, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wook-Jin","family":"Chae","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun D.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphys.2018.00373","article-title":"Development of the human placenta and fetal heart: Synergic or independent?","volume":"9","author":"Burton","year":"2018","journal-title":"Front. 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