{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:10:29Z","timestamp":1790471429420,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,3,27]],"date-time":"2019-03-27T00:00:00Z","timestamp":1553644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Adrenocortical carcinoma (ACC) is a rare endocrine cancer with treatments limited in efficacy for metastatic disease. New molecular targeted therapies have yet to improve patient outcomes. In contrast, established treatment regimens of adrenolytics and chemotherapy have demonstrated treatment benefit, although admittedly in a minority of patients. Identification of microRNAs (miRNAs) in patients responsive to adjuvant therapy may offer a means to sensitize patients with progressive disease to existing adjuvant regimens.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and Methods<\/jats:title>\n                  <jats:p>Samples from primary ACC tumors of 10 Stage IV patients were examined for differentially expressed miRNAs between a \u201csensitive\u201d and \u201cresistant\u201d cohort. Candidate microRNAs were restored via transfection in two functional ACC cell lines. Gain of function and effects on apoptosis and cell cycle were assessed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>microRNA-431 (miR-431) was underexpressed in patients with ACC with progressive disease undergoing adjuvant therapy. Restoration of miR-431 in vitro decreased the half maximal inhibitory concentrations of doxorubicin and mitotane, with markedly increased apoptosis. We found that a reversal of epithelial-mesenchymal transition underlies the action of miR-431 with doxorubicin treatment, with Zinc Finger E-Box Binding Homeobox 1 implicated as the molecular target of miR-431 in ACC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This is the first report of the potential of miRNA therapy to sensitize ACC to current established adjuvant therapy regimens, which may mitigate the resistance underlying treatment failure in patients with advanced ACC. Effective and well-studied methods of targeted miRNA delivery in existence hints at the imminent translatability of these findings.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2018-0849","type":"journal-article","created":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T10:40:37Z","timestamp":1553769637000},"page":"e241-e250","source":"Crossref","is-referenced-by-count":22,"title":["microRNA-431 as a Chemosensitizer and Potentiator of Drug Activity in Adrenocortical Carcinoma"],"prefix":"10.1093","volume":"24","author":[{"given":"Grace T.Y.","family":"Kwok","sequence":"first","affiliation":[{"name":"Cancer Genetics Laboratory, Kolling Institute, Northern Sydney Local Health District, St Leonards, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing Ting","family":"Zhao","sequence":"additional","affiliation":[{"name":"Cancer Genetics Laboratory, Kolling Institute, Northern Sydney Local Health District, St Leonards, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony R.","family":"Glover","sequence":"additional","affiliation":[{"name":"Cancer Genetics Laboratory, Kolling Institute, Northern Sydney Local Health District, St Leonards, New South Wales, Australia"},{"name":"Department of Endocrinology, Royal North Shore Hospital and University of Sydney, St Leonards, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Gill","sequence":"additional","affiliation":[{"name":"Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia"},{"name":"NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards and University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick","family":"Clifton-Bligh","sequence":"additional","affiliation":[{"name":"Cancer Genetics Laboratory, Kolling Institute, Northern Sydney Local Health District, St Leonards, New South Wales, Australia"},{"name":"Sydney Medical School Northern, Royal North Shore Hospital, University of Sydney, St Leonards, Sydney, New South Wales, Australia"},{"name":"Department of Endocrinology, Royal North Shore Hospital and University of Sydney, St Leonards, Sydney, New South Wales, Australia"},{"name":"University of Sydney Endocrine Surgery Unit, Royal North Shore Hospital, Sydney, St Leonards, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce G.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Cancer Genetics Laboratory, Kolling Institute, Northern Sydney Local Health District, St Leonards, New South Wales, Australia"},{"name":"Department of 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