{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T11:16:37Z","timestamp":1761218197442,"version":"3.37.3"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T00:00:00Z","timestamp":1572307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006364","name":"Institut National Du Cancer","doi-asserted-by":"publisher","award":["R01CA157881"],"award-info":[{"award-number":["R01CA157881"]}],"id":[{"id":"10.13039\/501100006364","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A prostate cancer risk single\u2010nucleotide polymorphism (SNP), rs13426236, is significantly associated with melanophilin (<jats:italic>MLPH<\/jats:italic>) expression. To functionally characterize role of the rs13426236 in prostate cancer, we first performed splicing\u2010specific expression quantitative trait loci analysis and refined the significant association of rs13426236 allele G with an increased expression of <jats:italic>MLPH<\/jats:italic> splicing transcript variant 4 (V4) (<jats:italic>P<\/jats:italic>\u2009=\u20097.61E\u22125) but not other protein\u2010coding variants (V1\u2010V3) (<jats:italic>P<\/jats:italic>\u2009&gt;\u2009.05). We then performed an allele\u2010specific reporter assay to determine if SNP\u2010containing sequences functioned as an active enhancer. Compared to allele A, allele G of rs13426236 showed significantly higher luciferase activity on the promoter of the splicing transcript V4 (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.03) but not on the promoter of transcript V1 (<jats:italic>P<\/jats:italic>\u2009&gt;\u2009.05) in two prostate cancer cell lines (DU145 and 22Rv1). Cell transfection assays showed stronger effect of transcript V4 than V1 on promoting cell proliferation, invasion, and antiapoptotic activities. RNA profiling analysis demonstrated that transcript V4 overexpression caused significant expression changes in glycosylation\/glycoprotein and metal\u2010binding gene ontology pathways (FDR\u2009&lt;\u20090.01). We also found that both transcripts V4 and V1 were significantly upregulated in prostate adenocarcinoma (<jats:italic>P<\/jats:italic>\u2009\u2264\u20092.49E\u22126) but only transcript V4 upregulation was associated with poor recurrence\u2010free survival (<jats:italic>P<\/jats:italic>\u2009=\u2009.028, hazard ratio\u2009=\u20091.63, 95% confidence interval\u2009=\u20091.05\u20102.42) in The Cancer Genome Atlas data. This study provides strong evidence showing that prostate cancer risk SNP rs13426236 upregulates expression of <jats:italic>MLPH<\/jats:italic> transcript V4, which may function as a candidate oncogene in prostate cancer.<\/jats:p>","DOI":"10.1002\/mc.23127","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T07:29:03Z","timestamp":1572334143000},"page":"45-55","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Single\u2010nucleotide polymorphism rs13426236 contributes to an increased prostate cancer risk via regulating <i>MLPH<\/i> splicing variant 4"],"prefix":"10.1002","volume":"59","author":[{"given":"Fankai","family":"Xiao","sequence":"first","affiliation":[{"name":"Henan Key Laboratory for Cancer Research The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan China"},{"name":"Department of Pathology, MCW Cancer Center Medical College of Wisconsin Milwaukee Wisconsin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, MCW Cancer Center Medical College of Wisconsin Milwaukee Wisconsin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, MCW Cancer Center Medical College of Wisconsin Milwaukee Wisconsin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yijun","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pathology, MCW Cancer Center Medical College of Wisconsin Milwaukee Wisconsin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"James","sequence":"additional","affiliation":[{"name":"Department of Surgery, MCW Cancer Center Medical College of Wisconsin Milwaukee Wisconsin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiang\u2010Ching","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Wisconsin Milwaukee Wisconsin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidong","family":"Wang","sequence":"additional","affiliation":[{"name":"Henan Key Laboratory for Cancer Research The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9364-8572","authenticated-orcid":false,"given":"Liang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, MCW Cancer Center Medical College of Wisconsin Milwaukee Wisconsin"},{"name":"Department of Tumor Biology H. Lee Moffitt Cancer Center and Research Institute Tampa Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,10,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-16-0237"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2014.0120"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-13-0568"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-419X(98)00030-4"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-16-1046"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0142-8"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23008"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9653"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11247"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14248"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1010-1045"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2416"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.137323.112"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-016-0556-9"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1107"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr917"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks542"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1235587"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq308"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12440"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5240"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.10520"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.06.003"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04451-x"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1002"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.882"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-148X.2009.00558.x"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202574200"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14646"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-016-0287-7"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22909"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1617467114"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1177\/117693510700300001"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.437749"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.23127","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mc.23127","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.23127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T05:03:05Z","timestamp":1693630985000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.23127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,29]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1002\/mc.23127"],"URL":"https:\/\/doi.org\/10.1002\/mc.23127","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"type":"print","value":"0899-1987"},{"type":"electronic","value":"1098-2744"}],"subject":[],"published":{"date-parts":[[2019,10,29]]},"assertion":[{"value":"2019-05-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}