Serums miR-24-3p and miR-1301-3p as potential biomarkers in MEN1 syndrome

Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary tumor syndrome caused by inactivating mutations of the MEN1 gene and characterized by the occurrence of multiple endocrine tumors within a single patient (i.e., parathyroid, pituitary, and pancreatic neuroendocrine tumors (NETs)). However, the lack of a genotype–phenotype correlation does not allow individual disease evolution to be foreseen. Epigenetic factors, such as microRNAs, are suspected to contribute to MEN1 tumorigenesis, presumably explaining the lack of genotype–phenotype association. Our previous studies indicated miR-24-3p, miR-1301-3p, miR-664a-3p, and miR-4258 as potentially involved in MEN1 parathyroid tumorigenesis. In this study, we examined the expression of two circulating microRNAs (c-miRNAs), miR-24-3p and miR-1301-3p, in the serum of MEN1 patients. c-miRNAs were evaluated by RT-qPCR in serum collected from 25MEN1patients and 25 age- and gender-matched healthy volunteers (HCs). Receiver operating characteristic (ROC) curves were constructed to determine miRNA sensitivity and specificity. RT-PCR analysis revealed that expression levels of circulating miR-1301-3p were significantly downregulated, while those of miR-24-3p were significantly upregulated in the serum of MEN1 patients compared to HCs. Additionally, ROC analysis exhibited a good diagnostic power for both miRNAs (area under the ROC curve (AUC) values: 0.7356 and 0.7928 for miR-1301-3p and miR-24-3p, respectively) in distinguishing MEN1 patients from matched HCs. These preliminary data suggest circulating miR-1301-3p and miR-24-3p as potential non-invasive diagnostic biomarkers for MEN1 syndrome, regardless of different clinical phenotypes and MEN1mutation types.