دورية أكاديمية

Overexpression of miR-375 and L-type Amino Acid Transporter 1 in Pheochromocytoma and Their Molecular and Functional Implications

التفاصيل البيبلوغرافية
العنوان: Overexpression of miR-375 and L-type Amino Acid Transporter 1 in Pheochromocytoma and Their Molecular and Functional Implications
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