The role of non-coding RNAs in the pathogenesis of multiple endocrine neoplasia syndrome type 1

Mamedova, Elizaveta; Dimitrova, Diana; Belaya, Zhanna; Мельниченко, Г. А.

doi:10.14341/probl12413

Cited by 5 publications

(2 citation statements)

References 57 publications

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“…Если у пациента с клиническими проявлениями МЭН-1 не удалось обнаружить мутацию в гене MEN1, то данное состояние считается фенокопией синдрома МЭН-1. Причина сочетания нескольких эндокринных МЭН-1-ассоциированных опухолей у таких пациентов остается не до конца изученной, и как возможное основание возникновения такого фенотипа могут быть рассмотрены мутации в таких генах, как CDKN1A, CDKN1B, CDKN2B, CDKN2C, CDC73, CASR, RET, AIP, других еще неизвестных генах, а также эпигенетические изменения или случайное сочетание нескольких опухолей у одного пациента [ 1 ][ 2 ][ 6 ][ 9 ].…”

Section: обоснованиеunclassified

Plasma miRNA expression in patients with genetically confirmed multiple endocrine neoplasia type 1 syndrome and its phenocopies

Trukhina,

Mamedova,

Nikitin

et al. 2024

Probl Endokrinol (Mosk)

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BACKGROUND: MEN-1 is a rare autosomal dominant disease caused by mutations in MEN1 gene encoding the menin protein. This syndrome is characterized by the occurrence of parathyroid tumors, gastroenteropancreatic neuroendocrine tumors, pituitary adenomas, as well as other endocrine and non-endocrine tumors. If a patient with the MEN-1 phenotype carry no mutations in the MEN1 gene, the condition considers a phenocopy of syndrome (phMEN1). The possible cause of this changes could be changes in epigenetic regulation, particularly in microRNA expression that might affect menin signaling pathways.AIM: to identify differently expressed circulating miRNAs in plasma in patients with genetically confirmed MEN-1 syndrome, its phenocopies and healthy controls.MATERIALS AND METHODS: single-center, case-control study was conducted. We assessed plasma microRNA expression in patients with genetically confirmed MEN-1 (gMEN1), phMEN1 and healthy controls. Morning plasma samples were collected from fasting patients and stored at –80°C. Total RNA isolation was performed using miRNeasy Mini Kit with QIAcube. The libraries were prepared by the QIAseq miRNA Library Kit following the manufacturer. Circulating miRNA sequencing was done on Illumina NextSeq 500 (Illumina). Subsequent data processing was performed using the DESeq2 bioinformatics algorithm.RESULTS: we enrolled 21 consecutive patients with gMEN1 and 11 patients with phMEN1, along with 12 gender matched controls. Median age of gMEN1 was 38,0 [34,0; 41,0]; in phMEN1 — 59,0 [51,0; 60,0]; control — 59,5 [51,5; 62,5]. The gMEN1 group differed in age (p<0.01) but not gender (р=0.739) or BMI (р=0.116) compared to phMEN1 and controls group, the last two groups did not differ by these parameters (p>0.05). 25 microRNA were differently expressed in groups gMEN1 and phMEN1 (21 upregulated microRNAs, 4 — downregulated). Comparison of samples from the phMEN-1 group and relatively healthy controls revealed 10 differently expressed microRNAs: 5 — upregulated; 5 — downregulated. In the gMEN-1 and control groups, 26 differently expressed microRNAs were found: 24 — upregulated; 2 — downregulated. The miRNAs most differing in expression among the groups were selected for further validation by RT-qPCR (in the groups of gMEN1 vs phMEN1 — miR-3613-5p, miR-335-5p, miR-32-5p, miR-425-3p, miR-25-5p, miR-576-5p, miR-215-5p, miR-30a-3p, miR-141-3p, miR-760, miR-501-3p; gMEN1 vs control — miR-1976, miR-144-5p miR-532-3p, miR-375; as well as in phMEN1 vs control — miR-944, miR-191-5p, miR-98-5p).CONCLUSION: In a pilot study, we detected microRNAs that may be expressed differently between patients with gMEN-1 and phMEN-1. The results need to be validated using different measurement method with larger sample size.

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Section: обоснованиеunclassified

Plasma miRNA expression in patients with genetically confirmed multiple endocrine neoplasia type 1 syndrome and its phenocopies

Trukhina,

Mamedova,

Nikitin

et al. 2024

Probl Endokrinol (Mosk)

Self Cite

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“…The MEN1 gene encodes the menin protein, which is a tumor suppressor, the inactivation of which leads to hyperplasia and tumor transformation of various organs and tissues. With this syndrome, combined tumor lesions of the parathyroid glands (PTG) (90%), the gastrointestinal tract (30-70%), including insulinoma, the adenohypophysis (30-40%) develop, besides others [5].…”

Section: Other Hereditary Disorders Of Glucose Metabolism With Insuli...mentioning

confidence: 99%

Clinical Case Report of Non-Diabetic Hypoglycemia Due to a Combination of Germline Mutations in the MEN1 and ABCC8 Genes

Yukina,

Solodovnikova,

Popov

et al. 2023

Genes

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Introduction: Non-diabetic hypoglycemia (NDH) is a collective term including the multiple causes of hypoglycemic syndrome not due to diabetes mellitus. NDH may result from insulinoma, IGF-2-omas, hypocorticism, Hirata’s disease, genital disorders of glucose metabolism, etc. One of the most common causes of NDH faced by an endocrinologist is insulinoma, which in turn can be part of the hereditary syndrome of multiple endocrine neoplasia type 1 (MEN1). Congenital disorders of glucose metabolism in adult patients, on the contrary, are diagnosed extremely rarely, since they usually manifest in childhood. This article presents a unique clinical case of a patient with NDH and genetically verified MEN1 in combination with congenital hyperinsulinism due to an ABCC8 gene mutation. Case Report: A 43-year-old patient with hypoglycemic symptoms from childhood is presented, in whom multiple pancreatic tumors and fluctuations in glycemia from 38.7 mg/dL to 329.7 mg/dL (2.15 to 18.3 mmol/L) were detected in adulthood, but a mild course of hypoglycemic syndrome was noted. Numerous examinations that were performed to establish an accurate diagnosis are described, signs that served as a reason for expanding the complex of studies are indicated, possible pathogenetic mechanisms of the mild course of hypoglycemic syndrome and hyperglycemic conditions are discussed. Conclusion: This case report is original and highlights that we must always remain intolerant of the inexplicable. Conducting an extended gene study can help perform a correct diagnosis in complex cases.

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Multiple endocrine neoplasia type 4 (MEN4): a thorough update on the latest and least known men syndrome

Ruggeri,

Benevento,

De Cicco

et al. 2023

Endocrine

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The role of non-coding RNAs in the pathogenesis of multiple endocrine neoplasia syndrome type 1

Cited by 5 publications

References 57 publications

Plasma miRNA expression in patients with genetically confirmed multiple endocrine neoplasia type 1 syndrome and its phenocopies

Plasma miRNA expression in patients with genetically confirmed multiple endocrine neoplasia type 1 syndrome and its phenocopies

Clinical Case Report of Non-Diabetic Hypoglycemia Due to a Combination of Germline Mutations in the MEN1 and ABCC8 Genes

Multiple endocrine neoplasia type 4 (MEN4): a thorough update on the latest and least known men syndrome

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