{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T21:24:34Z","timestamp":1771363474907,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T00:00:00Z","timestamp":1523923200000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81260128"],"award-info":[{"award-number":["81260128"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81100561"],"award-info":[{"award-number":["81100561"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81170732"],"award-info":[{"award-number":["81170732"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009102","name":"Education Department of Jiangxi Province","doi-asserted-by":"publisher","award":["GJJ12549"],"award-info":[{"award-number":["GJJ12549"]}],"id":[{"id":"10.13039\/501100009102","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Experimental Path"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The mechanism of aldosterone\u2010producing adrenocortical adenoma (<jats:styled-content style=\"fixed-case\">APA<\/jats:styled-content>) pathogenesis and the role of micro<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s (mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s) in <jats:styled-content style=\"fixed-case\">APA<\/jats:styled-content> pathogenesis have not been completely clarified. We examined the expression and function of miR\u2010140\u20103p, miR\u2010193a\u20103p and miR\u201022\u20103p, which have binding sites in <jats:italic><jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>11B2<\/jats:italic>. Expression of mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s and <jats:italic><jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>11B2 <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> was measured by quantitative reverse transcription <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">qRT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>). Cell proliferation was monitored by colorimetric analysis, and cell apoptosis and cell cycle progression were analysed by flow cytometry. <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content> was carried out to detect aldosterone levels in cell culture supernatants. Luciferase reporter assays, <jats:styled-content style=\"fixed-case\">qRT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> and Western blotting were performed to identify <jats:italic><jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>11B2<\/jats:italic> as a target of miR\u2010193a\u20103p. Of the three mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s examined, miR\u2010193a\u20103p exhibited a significant decrease and <jats:italic><jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>11B2 <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> exhibited a significant increase in expression in <jats:styled-content style=\"fixed-case\">APA<\/jats:styled-content> compared with adjacent normal adrenal gland tissue. Transfection of miR\u2010193a\u20103p mimic into the human adrenocortical cell line H295R showed that elevated miR\u2010193a\u20103p expression inhibits proliferation and aldosterone secretion, induces G1\u2010phase arrest and promotes apoptosis in H295R cells. Furthermore, in luciferase reporter assays, overexpression of miR\u2010193a\u20103p in H295R cells significantly reduced the luciferase activity of the wild\u2010type <jats:italic><jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>11B2<\/jats:italic> 3\u02b9\u2010<jats:styled-content style=\"fixed-case\">UTR<\/jats:styled-content> construct, which could be reversed by mutation of the miR\u2010193a\u20103p\u2010binding site. Moreover, miR\u2010193a\u20103p overexpression downregulated <jats:italic><jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>11B2 <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein expression. Finally, overexpression of <jats:italic><jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>11B2<\/jats:italic> diminished the effects of miR\u2010193a\u20103p on H295R cells. Taken together, our results suggest that <jats:italic><jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>11B2<\/jats:italic> levels may be modulated by miR\u2010193a\u20103p in <jats:styled-content style=\"fixed-case\">APA<\/jats:styled-content>, which could explain, at least partially, why downregulation of miR\u2010193a\u20103p during <jats:styled-content style=\"fixed-case\">APA<\/jats:styled-content> formation may promote cell growth and suppress apoptosis.<\/jats:p>","DOI":"10.1111\/iep.12267","type":"journal-article","created":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T18:21:22Z","timestamp":1523989282000},"page":"77-86","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["MiR\u2010193a\u20103p functions as a tumour suppressor in human aldosterone\u2010producing adrenocortical adenoma by down\u2010regulating <scp>CYP<\/scp>11B2"],"prefix":"10.1111","volume":"99","author":[{"given":"Guoxi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Urology First Affiliated Hospital of Gannan Medical University Ganzhou Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4211-9950","authenticated-orcid":false,"given":"Xiaofeng","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Urology First Affiliated Hospital of Gannan Medical University Ganzhou Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quanliang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology First Affiliated Hospital of Gannan Medical University Ganzhou Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianpeng","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Urology First Affiliated Hospital of Gannan Medical University Ganzhou Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruohui","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Urology First Affiliated Hospital of Gannan Medical University Ganzhou Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Urology First Affiliated Hospital of Gannan Medical University Ganzhou Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changfu","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Urology First Affiliated Hospital of Gannan Medical University Ganzhou Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaxing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Urology First Affiliated Hospital of Gannan Medical University Ganzhou Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,4,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2003.10.011"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.20325"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend-5-10-1513"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-4061"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12814"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.6.5.717"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep44137"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.12.035"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.621409"},{"key":"e_1_2_8_11_1","first-page":"124","article-title":"Characterization of NCI\u2010H295R cells as an in\u00a0vitro model of hyperaldosteronism","volume":"45","author":"Lichtenauer U.D.","year":"2013","journal-title":"Horm. Metab. Res."},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00060793-200106000-00004"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1210\/jcem.83.7.4946","article-title":"Diagnosis of glucocorticoid\u2010remediable aldosteronism in primary aldosteronism: aldosterone response to dexamethasone and long polymerase chain reaction for chimeric gene","volume":"83","author":"Mulatero P.","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2014.01.016"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.240.183"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2013.1896"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-3239"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.marpolbul.2014.04.002"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.01102"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-011-9162-8"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e3282f4b3e6"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ12-0270"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-1298"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2638"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1159\/000356605"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.01733"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.08313"}],"container-title":["International Journal of Experimental Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fiep.12267","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/iep.12267","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T12:10:04Z","timestamp":1694952604000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/iep.12267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1111\/iep.12267"],"URL":"https:\/\/doi.org\/10.1111\/iep.12267","archive":["Portico"],"relation":{},"ISSN":["0959-9673","1365-2613"],"issn-type":[{"value":"0959-9673","type":"print"},{"value":"1365-2613","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4]]},"assertion":[{"value":"2017-09-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}