{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T18:25:59Z","timestamp":1784053559568,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T00:00:00Z","timestamp":1591228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["AIRC, IG 17103)."],"award-info":[{"award-number":["AIRC, IG 17103)."]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007388","name":"Compagnia di San Paolo","doi-asserted-by":"publisher","award":["Prot. : 2017.AAI4504.U5092"],"award-info":[{"award-number":["Prot. : 2017.AAI4504.U5092"]}],"id":[{"id":"10.13039\/100007388","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Uveal melanoma (UM) is a rare tumor of the eye that leads to deadly metastases in about half of the patients. ADAM10 correlates with c-Met expression in UM and high levels of both molecules are related to the development of metastases. MiR122 and miR144 modulate ADAM10 and c-Met expression in different settings. We hypothesized a potential onco-suppressive role for miR122 and miR144 through modulation of ADAM10 and c-Met in UM. We analyzed the UM Cancer Genome Atlas data portal (TCGA) dataset, two other cohorts of primary tumors and five human UM cell lines for miR122 and miR144 expression by miR microarray, RT-qPCR, Western blotting, miR transfection and luciferase reporter assay. Our results indicate that miR122 and miR144 are expressed at low levels in the UM cell lines and in the TCGA UM dataset and were down-modulated in a cohort of seven UM samples, compared to normal choroid. Both miR122 and miR144 directly targeted ADAM10 and c-Met. Overexpression of miR122 and miR144 led to reduced expression of ADAM10 and c-Met in the UM cell lines and impaired cell proliferation, migration, cell cycle and shedding of c-Met ecto-domain. Our results show that miR122 and miR144 display an onco-suppressive role in UM through ADAM10 and c-Met modulation.<\/jats:p>","DOI":"10.3390\/cancers12061468","type":"journal-article","created":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T03:32:21Z","timestamp":1591327941000},"page":"1468","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Potential Onco-Suppressive Role of miR122 and miR144 in Uveal Melanoma through ADAM10 and C-Met Inhibition"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1573-7756","authenticated-orcid":false,"given":"Adriana","family":"Amaro","sequence":"first","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4683-4951","authenticated-orcid":false,"given":"Michela","family":"Croce","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvano","family":"Ferrini","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Barisione","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Gualco","sequence":"additional","affiliation":[{"name":"Azienda Sociosanitaria Ligure 3 (ASL3), Sistema Sanitario Regionale Liguria, 16149 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2538-8278","authenticated-orcid":false,"given":"Patrizia","family":"Perri","sequence":"additional","affiliation":[{"name":"Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto G. Gaslini|Ospedale Pediatrico Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0872-4671","authenticated-orcid":false,"given":"Ulrich","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2261-3820","authenticated-orcid":false,"given":"Martine J.","family":"Jager","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, 2333ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1464-2069","authenticated-orcid":false,"given":"Sarah E.","family":"Coupland","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L7 8TX, UK"},{"name":"Liverpool University Hospitals NHS Foundation Trust, Liverpool L7 8XP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Mosci","sequence":"additional","affiliation":[{"name":"Galliera Hospital, 16128 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilberto","family":"Filaci","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"},{"name":"Centre of Excellence for Biomedical Research and Department of Internal Medicine, University of Genoa, Via De Toni 14, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4203-2022","authenticated-orcid":false,"given":"Marina","family":"Fabbi","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Queirolo","sequence":"additional","affiliation":[{"name":"IEO Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaria","family":"Gangemi","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s10555-017-9663-3","article-title":"The biology of uveal melanoma","volume":"36","author":"Amaro","year":"2017","journal-title":"Cancer Metastasis Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1001\/jamaophthalmol.2014.77","article-title":"Age, survival predictors, and metastatic death in patients with choroidal melanoma: Tentative evidence of a therapeutic effect on survival","volume":"132","author":"Damato","year":"2014","journal-title":"JAMA Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1111\/aos.12432","article-title":"Response of patients with metastatic uveal melanoma to combined treatment with fotemustine and sorafenib","volume":"92","author":"Niederkorn","year":"2014","journal-title":"Acta Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/nature07586","article-title":"Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi","volume":"457","author":"Bezrookove","year":"2009","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1056\/NEJMoa1000584","article-title":"Mutations in GNA11 in uveal melanoma","volume":"363","author":"Griewank","year":"2010","journal-title":"N. 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