{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:20:36Z","timestamp":1791490836963,"version":"4.3.4"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The human choriocarcinoma cell line JEG\u20103 offers a valuable model to study galectin\u201016 gene (<jats:italic>LGALS16<\/jats:italic>) expression and functions in the context of placental cell differentiation and cancer cell biology. Recent evidence indicates that cAMP\u2010mediated signaling pathways might be responsible for the upregulation of <jats:italic>LGALS16<\/jats:italic>; however, the underlying mechanisms are unknown. Here, we employed biochemical inhibitors of the cAMP cascade and CRISPR\/Cas9 engineered cells to assess regulatory patterns and associations between cAMP\u2010induced trophoblast differentiation and <jats:italic>LGALS16<\/jats:italic> expression in JEG\u20103 cells. The expression of <jats:italic>LGALS16<\/jats:italic> was significantly upregulated in parallel with human chorionic gonadotropin beta (CGB), a biomarker of syncytiotrophoblast differentiation, in response to 8\u2010Br\u2010cAMP. Inhibition of p38 MAPK and EPAC significantly altered <jats:italic>LGALS16<\/jats:italic> expression during differentiation, while PKA inhibition failed to change <jats:italic>LGALS16<\/jats:italic> and <jats:italic>CGB3\/5<\/jats:italic> expression in our cell model. The CRISPR\/Cas9 <jats:italic>LGALS16<\/jats:italic> knockout cell pool expressed a significantly lower amount of <jats:italic>CGB3\/5<\/jats:italic>, a reduced level of CGB protein, and an unaltered cell growth rate in response to 8\u2010Br\u2010cAMP in comparison with wild\u2010type JEG\u20103 cells. Collectively, these findings suggest that <jats:italic>LGALS16<\/jats:italic> is required for the trophoblast\u2010like differentiation of JEG\u20103 cells, and its expression is mediated through p38 MAPK and EPAC signaling pathway branches.<\/jats:p>","DOI":"10.1002\/cbin.12128","type":"journal-article","created":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T05:21:26Z","timestamp":1705036886000},"page":"378-385","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Insights into cAMP\u2010dependent molecular mechanisms regulating expression and function of <i>LGALS16<\/i> gene in choriocarcinoma JEG\u20103 cells"],"prefix":"10.1002","volume":"48","author":[{"given":"Jennifer D.","family":"Kaminker","sequence":"first","affiliation":[{"name":"Department of Biology The University of Western Ontario London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad G.","family":"Butt","sequence":"additional","affiliation":[{"name":"Department of Biology The University of Western Ontario London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailey","family":"Killeen","sequence":"additional","affiliation":[{"name":"Department of Biology The University of Western Ontario London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4237-513X","authenticated-orcid":false,"given":"Alexander V.","family":"Timoshenko","sequence":"additional","affiliation":[{"name":"Department of Biology The University of Western Ontario London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01166"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)38931-7"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-11-30"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-8-102"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-19-0539"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20100323"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2010.10.013"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2015.02.002"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1023\/b:mcbi.0000049376.50242.7f"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2015.00202"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12436"},{"key":"e_1_2_10_13_1","first-page":"895","article-title":"Tumor suppressor genes as negative growth regulators in development and differentiation","volume":"39","author":"Gutmann D. 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