{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:34:31Z","timestamp":1792467271606,"version":"4.5.0"},"reference-count":69,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003339","name":"Spanish Ministry of Science, Innovation and Universities","doi-asserted-by":"publisher","award":["RTI2018-096915-B100"],"award-info":[{"award-number":["RTI2018-096915-B100"]}],"id":[{"id":"10.13039\/501100003339","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003339","name":"Spanish Ministry of Science, Innovation and Universities","doi-asserted-by":"publisher","award":["PID2021-122898OB-100"],"award-info":[{"award-number":["PID2021-122898OB-100"]}],"id":[{"id":"10.13039\/501100003339","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Regional Development Fund\/European Social Fund","award":["RTI2018-096915-B100"],"award-info":[{"award-number":["RTI2018-096915-B100"]}]},{"name":"European Regional Development Fund\/European Social Fund","award":["PID2021-122898OB-100"],"award-info":[{"award-number":["PID2021-122898OB-100"]}]},{"DOI":"10.13039\/501100003339","name":"ERDF A way of making Europe","doi-asserted-by":"publisher","award":["RTI2018-096915-B100"],"award-info":[{"award-number":["RTI2018-096915-B100"]}],"id":[{"id":"10.13039\/501100003339","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003339","name":"ERDF A way of making Europe","doi-asserted-by":"publisher","award":["PID2021-122898OB-100"],"award-info":[{"award-number":["PID2021-122898OB-100"]}],"id":[{"id":"10.13039\/501100003339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Activating mutations in KIT (CD117) have been associated with several diseases, including gastrointestinal stromal tumors and mastocytosis. Rapidly progressing pathologies or drug resistance highlight the need for alternative treatment strategies. Previously, we reported that the adaptor molecule SH3 binding protein 2 (SH3BP2 or 3BP2) regulates KIT expression at the transcriptional level and microphthalmia-associated transcription factor (MITF) expression at the post-transcriptional level in human mast cells and gastrointestinal stromal tumor (GIST) cell lines. Lately, we have found that the SH3BP2 pathway regulates MITF through miR-1246 and miR-5100 in GIST. In this study, miR-1246 and miR-5100 were validated by qPCR in the SH3BP2-silenced human mast cell leukemia cell line (HMC-1). MiRNA overexpression reduces MITF and MITF-dependent target expression in HMC-1. The same pattern was observed after MITF silencing. In addition, MITF inhibitor ML329 treatment reduces MITF expression and affects the viability and cell cycle progression in HMC-1. We also examine whether MITF downregulation affected IgE-dependent mast cell degranulation. MiRNA overexpression, MITF silencing, and ML329 treatment reduced IgE-dependent degranulation in LAD2- and CD34+-derived mast cells. These findings suggest MITF may be a potential therapeutic target for allergic reactions and deregulated KIT mast-cell-mediated disorders.<\/jats:p>","DOI":"10.3390\/ijms24043515","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T02:56:13Z","timestamp":1675997773000},"page":"3515","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["MITF Downregulation Induces Death in Human Mast Cell Leukemia Cells and Impairs IgE-Dependent Degranulation"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0185-3414","authenticated-orcid":false,"given":"Elizabeth","family":"Proa\u00f1o-P\u00e9rez","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Biology Unit, Biomedicine Department, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Clinical and Experimental Respiratory Immunoallergy (IRCE), Institut d\u2019Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Faculty of Health Sciences, Technical University of Ambato, Ambato 180105, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laia","family":"Oll\u00e9","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Unit, Biomedicine Department, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Clinical and Experimental Respiratory Immunoallergy (IRCE), Institut d\u2019Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanru","family":"Guo","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Unit, Biomedicine Department, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Clinical and Experimental Respiratory Immunoallergy (IRCE), Institut d\u2019Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8692-6482","authenticated-orcid":false,"given":"Cristina","family":"Aparicio","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Unit, Biomedicine Department, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9912-661X","authenticated-orcid":false,"given":"Mario","family":"Guerrero","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Unit, Biomedicine Department, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8566-8285","authenticated-orcid":false,"given":"Rosa","family":"Mu\u00f1oz-Cano","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Respiratory Immunoallergy (IRCE), Institut d\u2019Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Allergy Department, Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain"},{"name":"RICORS, Instituto de Salud Carlos III, 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9245-4899","authenticated-orcid":false,"given":"Margarita","family":"Martin","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Unit, Biomedicine Department, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Clinical and Experimental Respiratory Immunoallergy (IRCE), Institut d\u2019Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"RICORS, Instituto de Salud Carlos III, 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1182\/blood-2016-09-731893","article-title":"Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts","volume":"129","author":"Valent","year":"2017","journal-title":"Blood"},{"key":"ref_2","first-page":"686","article-title":"Mastocytosis\u2014A Disease of the Hematopoietic Stem Cell","volume":"105","author":"Horny","year":"2008","journal-title":"Dtsch. 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