دورية أكاديمية
Overexpression of miR-375 and L-type Amino Acid Transporter 1 in Pheochromocytoma and Their Molecular and Functional Implications
العنوان: | Overexpression of miR-375 and L-type Amino Acid Transporter 1 in Pheochromocytoma and Their Molecular and Functional Implications |
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المؤلفون: | Manso J., Bertazza L., Barollo S., Mondin A., Censi S., Carducci S., Ferrara A. M., Boschin I. M., Zovato S., Schiavi F., Gregianin M., Pennelli G., Iacobone M., Mian C. |
المساهمون: | Manso, J., Bertazza, L., Barollo, S., Mondin, A., Censi, S., Carducci, S., Ferrara, A. M., Boschin, I. M., Zovato, S., Schiavi, F., Gregianin, M., Pennelli, G., Iacobone, M., Mian, C. |
بيانات النشر: | MDPI |
سنة النشر: | 2022 |
المجموعة: | Padua Research Archive (IRIS - Università degli Studi di Padova) |
مصطلحات موضوعية: | 18F-dihydroxyphenylalanine, L-type amino acid transporter, MicroRNA, MiR-375, Pheochromocytoma, Adaptor Proteins, Signal Transducing, Adrenal Gland Neoplasm, Adult, Aged, 80 and over, Dihydroxyphenylalanine, Female, Gene Expression Regulation, Neoplastic, Human, Large Neutral Amino Acid-Transporter 1, Male, Middle Aged, Norepinephrine, Phenylethanolamine N-Methyltransferase, Positron-Emission Tomography, Retrospective Studie, Tumor Burden, Up-Regulation, Wnt Signaling Pathway |
الوصف: | 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 between18 F-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, performing18 F-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 between18 F-DOPA-PET SUV mean and LAT1 gene expression and for 24 h-urinary norepinephrine and LAT1. This is the first experimental evidence of18 F-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. |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/35269556; info:eu-repo/semantics/altIdentifier/wos/WOS:000774365700001; volume:23; issue:5; firstpage:2413; journal:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; http://hdl.handle.net/11577/3444245Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85125105272 |
DOI: | 10.3390/ijms23052413 |
الإتاحة: | https://doi.org/10.3390/ijms23052413Test http://hdl.handle.net/11577/3444245Test |
حقوق: | info:eu-repo/semantics/openAccess |
رقم الانضمام: | edsbas.F5E22FDB |
قاعدة البيانات: | BASE |
DOI: | 10.3390/ijms23052413 |
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