{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:07:58Z","timestamp":1791475678893,"version":"4.3.4"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,2,14]],"date-time":"2013-02-14T00:00:00Z","timestamp":1360800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:p>\n                    Achaete scute\u2010like 2 (\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">ASCL<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    ), a basic helix\u2010loop\u2010helix transcription factor, plays an essential role in the maintenance of adult intestinal stem cells. However, the function of\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">ASCL<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    in gastric cancer (\n                    <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\n                    ) is poorly understood. Therefore, we investigated the roles and regulatory transcription mechanisms of\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">ASCL<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    in\n                    <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\n                    . Gene expression and methylation data analysis showed that\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">ASCL<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    was upregulated and hypomethylated in\n                    <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\n                    tissues. Using real\u2010time\n                    <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>\n                    and pyrosequencing analysis, we confirmed that\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">ASCL<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    was overexpressed and hypomethylated in\n                    <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\n                    tissues compared to adjacent normal tissues. We then investigated the mechanisms underlying the aberrant expression of\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">ASCL<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    in\n                    <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\n                    and found that treatment with a methylation inhibitor induced\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">ASCL<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    expression in\n                    <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\n                    cell lines.\n                    <jats:styled-content style=\"fixed-case\">MBD<\/jats:styled-content>\n                    \u2010sequencing assay also revealed hypermethylation of the promoter region of\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">ASCL<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    in\n                    <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\n                    cell lines, which barely expressed the\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">ASCL<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    gene. Furthermore,\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">ASCL<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    expression levels were inversely correlated with\n                    <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\n                    patient survival. Ectopic overexpression of\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">ASCL<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    showed that\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">ASCL<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    increased cell growth and promoted resistance to 5\u2010fluorouracil in\n                    <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\n                    cells. These results suggest that\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">ASCL<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    might play an important role in gastric tumor growth and chemoresistance, and could be a useful prognostic marker for\n                    <jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\n                    patients.\n                  <\/jats:p>","DOI":"10.1111\/cas.12076","type":"journal-article","created":{"date-parts":[[2012,11,26]],"date-time":"2012-11-26T23:48:03Z","timestamp":1353973683000},"page":"391-397","source":"Crossref","is-referenced-by-count":39,"title":["Aberrant upregulation of\n                    <i>\n                      <scp>ASCL<\/scp>\n                      2\n                    <\/i>\n                    by promoter demethylation promotes the growth and resistance to 5\u2010fluorouracil of gastric cancer cells"],"prefix":"10.1111","volume":"104","author":[{"given":"Oh\u2010Hyung","family":"Kwon","sequence":"first","affiliation":[{"name":"Medical Genomics Research Center Korea Research Institute of Bioscience and Biotechnology Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong\u2010Lyul","family":"Park","sequence":"additional","affiliation":[{"name":"Medical Genomics Research Center Korea Research Institute of Bioscience and Biotechnology Daejeon Korea"},{"name":"Department of Functional Genomics University of Science and Technology Korea Research Institute of Bioscience and Biotechnology Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su\u2010Jin","family":"Baek","sequence":"additional","affiliation":[{"name":"Medical Genomics Research Center Korea Research Institute of Bioscience and Biotechnology Daejeon Korea"},{"name":"Department of Functional Genomics University of Science and Technology Korea Research Institute of Bioscience and Biotechnology Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung\u2010Moo","family":"Noh","sequence":"additional","affiliation":[{"name":"Department of General Surgery College of Medicine Chungnam National University Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu\u2010Sang","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pathology Chungnam National University Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon\u2010Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Medical Genomics Research Center Korea Research Institute of Bioscience and Biotechnology Daejeon Korea"},{"name":"Department of Functional Genomics University of Science and Technology Korea Research Institute of Bioscience and Biotechnology Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Sung","family":"Kim","sequence":"additional","affiliation":[{"name":"Medical Genomics Research Center Korea Research Institute of Bioscience and Biotechnology Daejeon Korea"},{"name":"Department of Functional Genomics University of Science and Technology Korea Research Institute of Bioscience and Biotechnology Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,2,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990315)80:6<827::AID-IJC6>3.0.CO;2-P"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1141"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1279"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncponc0354"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205651"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.02.082"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2008.270"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C400479200"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.2.429-440.2000"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000134364"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.031"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209382"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032170"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2137"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0905653106"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-2638"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.4137\/CIN.S7226"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2010.12.002"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2011.10.008"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/35102167"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.019"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1164270"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.338"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605064"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-06-0684"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606599104"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djj495"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2012.40"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03319"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035486"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-1180"}],"container-title":["Cancer 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