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- Title
Overexpression of miR-375 and L-type Amino Acid Transporter 1 in Pheochromocytoma and Their Molecular and Functional Implications.
- Authors
Manso, Jacopo; Bertazza, Loris; Barollo, Susi; Mondin, Alberto; Censi, Simona; Carducci, Sofia; Ferrara, Alfonso Massimiliano; Boschin, Isabella Merante; Zovato, Stefania; Schiavi, Francesca; Gregianin, Michele; Pennelli, Gianmaria; Iacobone, Maurizio; Mian, Caterina
- Abstract
Pheochromocytoma (Pheo) is a tumor derived from chromaffin cells. It can be studied using 18F-dihydroxyphenylalanine (DOPA)—positron 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.
- Subjects
YAP signaling proteins; AMINO acids; PHEOCHROMOCYTOMA; GENETIC overexpression; POSITRON emission tomography; MONOCARBOXYLATE transporters
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 5, p2413
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23052413