{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:02:50Z","timestamp":1777377770498,"version":"3.51.4"},"reference-count":42,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pheochromocytoma (Pheo) is a tumor derived from chromaffin cells. It can be studied using 18F-dihydroxyphenylalanine (DOPA)\u2014positron emission tomography (PET) due to its overexpression of L-type amino acid transporters (LAT1 and LAT2). The oncogenic pathways involved are still poorly understood. This study examined the relationship between 18F-DOPA-PET uptake and LAT1 expression, and we explored the role of miR-375 and putative target genes. A consecutive series of 58 Pheo patients were retrospectively analyzed, performing 18F-DOPA-PET in 32\/58 patients. Real-time quantitative PCR was used to assess the expression of LAT1, LAT2, phenylethanolamine N-methyltransferase (PNMT), miR-375, and the major components of the Hippo and Wingless\/Integrated pathways. Principal germline mutations associated with hereditary Pheo were also studied. Pheo tissues had significantly higher LAT1, LAT2, and PNMT mRNA levels than normal adrenal tissues. MiR-375 was strongly overexpressed. Yes-associated protein 1 and tankyrase 1 were upregulated, while beta-catenin, axin2, monocarboxylate transporter 8, and Frizzled 8 were downregulated. A positive relationship was found between 18F-DOPA-PET SUV mean and LAT1 gene expression and for 24 h-urinary norepinephrine and LAT1. This is the first experimental evidence of 18F-DOPA uptake correlating with LAT1 overexpression. We also demonstrated miR-375 overexpression and downregulated (Wnt) signaling and identified the Hippo pathway as a new potentially oncogenic feature of Pheo.<\/jats:p>","DOI":"10.3390\/ijms23052413","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T22:34:30Z","timestamp":1645569270000},"page":"2413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Overexpression of miR-375 and L-type Amino Acid Transporter 1 in Pheochromocytoma and Their Molecular and Functional Implications"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2403-4339","authenticated-orcid":false,"given":"Jacopo","family":"Manso","sequence":"first","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), Padua University, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loris","family":"Bertazza","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), Padua University, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5821-2693","authenticated-orcid":false,"given":"Susi","family":"Barollo","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), Padua University, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Mondin","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), Padua University, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6946-9673","authenticated-orcid":false,"given":"Simona","family":"Censi","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), Padua University, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Carducci","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), Padua University, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5835-1709","authenticated-orcid":false,"given":"Alfonso Massimiliano","family":"Ferrara","sequence":"additional","affiliation":[{"name":"Familial Cancer Clinic and Oncoendocrinology, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella Merante","family":"Boschin","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), Padua University, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Zovato","sequence":"additional","affiliation":[{"name":"Familial Cancer Clinic and Oncoendocrinology, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Schiavi","sequence":"additional","affiliation":[{"name":"Familial Cancer Clinic and Oncoendocrinology, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Gregianin","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Unit, Veneto Institute of Oncology IOV-IRCCS, 31100 Treviso, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianmaria","family":"Pennelli","sequence":"additional","affiliation":[{"name":"Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), Padua University, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6057-4642","authenticated-orcid":false,"given":"Maurizio","family":"Iacobone","sequence":"additional","affiliation":[{"name":"Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), Padua University, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2615-8001","authenticated-orcid":false,"given":"Caterina","family":"Mian","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), Padua University, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1210\/jc.2014-1498","article-title":"Pheochromocytoma and Paraganglioma: An Endocrine Society Clinical Practice Guideline","volume":"99","author":"Lenders","year":"2014","journal-title":"J. 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