{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T02:19:57Z","timestamp":1773886797915,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,12,18]],"date-time":"2019-12-18T00:00:00Z","timestamp":1576627200000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Although chemotherapy is a core treatment for esophageal cancer, some patients develop drug resistance. Gene screening with transposons (i.e. mobile genetic elements) is a novel procedure for identifying chemotherapy\u2010resistant genes. Transposon insertion can randomly affect nearby gene expression. By identifying the affected genes, candidate genes can be found. The present study aimed to identify cisplatin (CDDP)\/5\u2010fluorouracil (5\u2010FU)\u2010resistant genes in <jats:italic>in vitro<\/jats:italic> human esophageal squamous cell carcinoma with transposons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>After establishing transposon\u2010tagged cells, we obtained CDDP\/5\u2010FU\u2010resistant colonies. A polymerase chain reaction and sequencing were used to identify the transposon inserted site and candidate CDDP\/5\u2010FU resistant genes. Focusing on one candidate gene, we confirmed CDDP\/5\u2010FU resistance by comparing the IC<jats:sub>50<\/jats:sub> between drug\u2010resistant and wild\u2010type cells. Furthermore, we investigated gene expression by a real\u2010time polymerase chain reaction. Finally, we mediated the candidate gene level with small interfering RNA to confirm the resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010nine candidate genes for CDDP\/5\u2010FU resistance were identified. Nineteen were for CDDP resistance and 27 were for 5\u2010FU resistance. Seven genes, THUMP domain\u2010containing protein 2 (<jats:italic>THUMPD2<\/jats:italic>), nuclear factor interleukin\u20103\u2010regulated protein (<jats:italic>NFIL3<\/jats:italic>), tyrosine\u2010protein kinase transmembrane receptor 2 (<jats:italic>ROR2<\/jats:italic>), C\u2010X\u2010C chemokine receptor type 4 (<jats:italic>CXCR4<\/jats:italic>), thrombospondin type\u20101 domain\u2010containing protein 2 (<jats:italic>THSD7B<\/jats:italic>) alpha\u2010parvin (<jats:italic>PARVA<\/jats:italic>) and TEA domain transcription factor 1 (<jats:italic>TEAD1<\/jats:italic>), were detected as candidate genes in both colonies. Regarding <jats:italic>THUMPD2<\/jats:italic>, its expression was downregulated and knocking down <jats:italic>THUMPD2<\/jats:italic> suggested drug resistance in both drugs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Thirty\u2010nine candidate genes were identified with transposons. The downregulation of THUMPD2 was suggested to play a role in multidrug resistance in in <jats:italic>vitro<\/jats:italic> esophageal squamous cell carcinoma.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3135","type":"journal-article","created":{"date-parts":[[2019,10,27]],"date-time":"2019-10-27T01:09:00Z","timestamp":1572138540000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["THUMP domain containing 2 protein possibly induces resistance to cisplatin and 5\u2010fluorouracil in <i>in vitro<\/i> human esophageal squamous cell carcinoma cells as revealed by transposon activation mutagenesis"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2437-056X","authenticated-orcid":false,"given":"Masato","family":"Hayashi","sequence":"first","affiliation":[{"name":"Department of Surgery Keio University, School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Kawakubo","sequence":"additional","affiliation":[{"name":"Department of Surgery Keio University, School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazumasa","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Surgery Keio University, School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuhei","family":"Mayanagi","sequence":"additional","affiliation":[{"name":"Department of Surgery Keio University, School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rieko","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Surgery Keio University, School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Suda","sequence":"additional","affiliation":[{"name":"Department of Surgery Fujita Health University Hospital  Toyoake Aichi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Testu","family":"Hayashida","sequence":"additional","affiliation":[{"name":"Department of Surgery Keio University, School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norihito","family":"Wada","sequence":"additional","affiliation":[{"name":"Department of Surgery Keio University, School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Kitagawa","sequence":"additional","affiliation":[{"name":"Department of Surgery Keio University, School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,12,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.48"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000357189"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2015.0028"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.12.095"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-011-2049-9"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(97)00356-0"},{"key":"e_1_2_9_8_1","first-page":"65","article-title":"Establishment and biological analysis of the EC109\/CDDP multidrug\u2010resistant esophageal squamous cell carcinoma cell line","volume":"22","author":"Wen J","year":"2009","journal-title":"Oncol Rep"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000146864"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11067"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-013-2983-9"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i40.14904"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-13-93"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2015.3085"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.6699"},{"key":"e_1_2_9_16_1","unstructured":"National Institute of Biomedical Innovation Health and Nutrition JCRB Cell Bank KYSE 2400. 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