{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:55Z","timestamp":1784557255515,"version":"3.55.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,1]]},"abstract":"\n Tumors of the parathyroid glands are highly vascularized and display a microRNA (miRNA) profile divergent from normal parathyroid glands (PaNs). Angiogenic miRNAs, namely miR-126-3p, miR-126-5p, and miR-296-5p, have been found downregulated in parathyroid tumors. Here, we show that miR-126-3p expression levels are reduced in parathyroid adenomas (PAds;\n n<\/jats:italic>\n = 12) compared with PaNs (\n n<\/jats:italic>\n = 4).\n In situ<\/jats:italic>\n hybridization (ISH) of miR-126-3p and miR-296-5p in 10 PAds show that miR-126-3p is expressed by endothelial cells lining the walls of great vessels and by cells within the thin stroma surrounding acinar structures. At variance, miR-296-5p was detectable in most PAd epithelial cells. Combining ISH for miR-126-3p with immunohistochemistry for the endothelial and mesenchymal markers CD34, CD31 and \u03b1-smooth muscle actin (\u03b1SMA), we could identify that miR-126-3p is localized in the \u03b1SMA-positive thin stroma. Further, miR-126-3p-expressing cells are enriched in the CD34-positive stromal cells surrounding epithelial cell acinar structures, a cellular pattern consistent with tumor-associated myofibroblasts (TAMs). In line with this, CD34-positive cells, sorted by FACS from PAds tissues, express miR-126-3p at higher levels than CD34-negative cells, suggesting that miR-126-3p downregulation promotes the endothelial-to-\u03b1SMA+ mesenchymal transition. In human mesenchymal stem cells derived from bone marrow (hBM-MSCs), a model of TAMs, the co-culture with PAds-derived cells for 5 days decreases miR-126-3p, while it increases\n VEGFA<\/jats:italic>\n expression. At variance, adrenomedullin (\n ADM<\/jats:italic>\n ) expression is unaffected. Finally, overexpression of the miR-126-3p mimic in both hBM-MSCs and PAds-derived explants downregulates\n VEGFA<\/jats:italic>\n expression levels. In conclusion, miR-126-3p is expressed by both endothelial cells and TAMs in PAds, and its downregulation promotes neoangiogenesis, possibly through\n VEGFA<\/jats:italic>\n overexpression.\n <\/jats:p>","DOI":"10.1530\/erc-20-0313","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T05:20:20Z","timestamp":1604553620000},"page":"53-63","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":6,"title":["miR-126-3p contributes to parathyroid tumor angiogenesis"],"prefix":"10.1530","volume":"28","author":[{"given":"Chiara","family":"Verdelli","sequence":"first","affiliation":[{"name":"1Laboratory of Experimental Endocrinology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Forno","sequence":"additional","affiliation":[{"name":"2Department of Pathophysiology and Organ Transplantation, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Morotti","sequence":"additional","affiliation":[{"name":"2Department of Pathophysiology and Organ Transplantation, University of Milan, Milan, Italy"},{"name":"4Endocrine Surgery, IRCCS Ospedale San Raffaele, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Maggiore","sequence":"additional","affiliation":[{"name":"5Endocrine Surgery, IRCCS Istituto Auxologico Italiano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilberto","family":"Mari","sequence":"additional","affiliation":[{"name":"5Endocrine Surgery, IRCCS Istituto Auxologico Italiano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Vicentini","sequence":"additional","affiliation":[{"name":"3Division of Pathology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Ferrero","sequence":"additional","affiliation":[{"name":"4Endocrine Surgery, IRCCS Ospedale San Raffaele, Milan, Italy"},{"name":"6Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Kuhn","sequence":"additional","affiliation":[{"name":"4Endocrine Surgery, IRCCS Ospedale San Raffaele, Milan, Italy"},{"name":"6Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Vaira","sequence":"additional","affiliation":[{"name":"2Department of Pathophysiology and Organ Transplantation, University of Milan, Milan, Italy"},{"name":"3Division of Pathology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Corbetta","sequence":"additional","affiliation":[{"name":"6Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy"},{"name":"7Endocrinology and Diabetology Service, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/28\/1\/ERC-20-0313.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/28\/1\/ERC-20-0313.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:55:48Z","timestamp":1784555748000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/28\/1\/53-63\/25468"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":0,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1530\/erc-20-0313","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]}}}