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Overexpression of miR-375 and L-type Amino Acid Transporter 1 in Pheochromocytoma and Their Molecular and Functional Implications.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2022 Feb 22; Vol. 23 (5). Date of Electronic Publication: 2022 Feb 22. - Publication Year :
- 2022
-
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 <superscript>18</superscript> 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, performing <superscript>18</superscript> 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 between <superscript>18</superscript> F-DOPA-PET SUV mean and LAT1 gene expression and for 24 h-urinary norepinephrine and LAT1. This is the first experimental evidence of <superscript>18</superscript> 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.
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Adrenal Gland Neoplasms genetics
Adrenal Gland Neoplasms pathology
Adrenal Gland Neoplasms urine
Adult
Aged
Aged, 80 and over
Dihydroxyphenylalanine administration & dosage
Dihydroxyphenylalanine analogs & derivatives
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Middle Aged
Norepinephrine urine
Phenylethanolamine N-Methyltransferase genetics
Pheochromocytoma genetics
Pheochromocytoma pathology
Pheochromocytoma urine
Retrospective Studies
Tumor Burden
Up-Regulation
Wnt Signaling Pathway
Adrenal Gland Neoplasms diagnostic imaging
Large Neutral Amino Acid-Transporter 1 genetics
MicroRNAs genetics
Pheochromocytoma diagnostic imaging
Positron-Emission Tomography methods
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 23
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 35269556
- Full Text :
- https://doi.org/10.3390/ijms23052413