MEN1 mutations and potentially MEN1-targeting miRNAs are responsible for menin deficiency in sporadic and MEN1 syndrome-associated primary hyperparathyroidism

Grolmusz, Vince; Borka, Katalin; Kövesdi, Annamária; Németh, Krisztián; Balogh, Katalin; Dekany, Csaba; Kiss, András; Szentpéteri, Anna; Sármán, Beatrix; Somogyi, Anikó; Csajbók, Éva; Valkusz, Zsuzsanna; Tóth, Miklós; Igaz, Péter; Rácz, Kàroly; Patócs, Attila

doi:10.1007/s00428-017-2158-3

Cited by 20 publications

(25 citation statements)

References 40 publications

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“…Grolmusz et al . also reported miR-24 and miR-28 were differentially expressed between sporadic and MEN1 parathyroid tumors 31 . Subsequently, miR-4258, miR-664, and miR-1301 were demonstrated to involve in the MEN1 associated parathyroid tumors 32 .…”

Section: Discussionmentioning

confidence: 88%

Differential expression of miRNA199b-5p as a novel biomarker for sporadic and hereditary parathyroid tumors

Hwang

Jeong

Kim

et al. 2018

Sci Rep

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MicroRNAs (miRNAs) are dysregulated in many tumors; however, miRNA regulation in parathyroid tumors remains poorly understood. To identify differentially expressed miRNAs between sporadic and hereditary parathyroid tumors and to analyze their correlation with clinicopathological features, a microarray containing 887 miRNAs was performed; then, the differentially expressed miRNAs were validated by qRT-PCR using 25 sporadic and 12 hereditary parathyroid tumors and 24 normal parathyroid tissue samples. A receiver operating characteristic curve (ROC) analysis was applied to evaluate the utility of the miRNAs for distinguishing parathyroid tumor types. Compared to the miRNAs in the normal parathyroid tissues, 10 miRNAs were differentially expressed between the sporadic and hereditary parathyroid tumors. Seven of these miRNAs (let-7i, miR-365, miR-125a-3p, miR-125a-5p, miR-142-3p, miR-193b, and miR-199b-5p) were validated in the parathyroid tumor samples. Among these miRNAs, only miR-199b-5p was differentially expressed (P < 0.001); miR-199b-5p was significantly downregulated and negatively associated with PTH levels (γ = −0.579, P = 0.002) in the sporadic tumors but was upregulated in the hereditary tumors. This miRNA showed 67% sensitivity and 100% specificity for distinguishing sporadic and hereditary parathyroid tumors. These results reveal altered expression of a miRNA between sporadic and hereditary parathyroid tumors and the potential role of miR-199b-5p as a novel biomarker for distinguishing these two types of parathyroid tumors.

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Section: Discussionmentioning

confidence: 88%

Differential expression of miRNA199b-5p as a novel biomarker for sporadic and hereditary parathyroid tumors

Hwang

Jeong

Kim

et al. 2018

Sci Rep

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“…Several layers of evidence confirmed the role of tissue-specific miRNA expression alterations in the pathogenesis of various tumors (9). As miRNAs are chemically more stable compared to mRNAs, miRNA expression can optimally be measured from formalin-fixed, paraffin-embedded samples (10,11,12), as it correlates well with expression levels obtained from fresh frozen specimens (11).…”

Section: Introductionmentioning

confidence: 93%

“…Total RNA was isolated from formalin-fixed, paraffinembedded sections using Ambion RecoverAll Total Nucleic Acid Isolation kit for FFPE tissues (Thermo Fisher Scientific) as earlier reported (10). Five nanograms of total RNA was reverse transcribed using single tube TaqMan microRNA assays (assay IDs: hsa-miR-21: 000397; hsa-miR-29a: 002112; hsa-miR-10a: 000387; hsa-miR-106b: 000442; hsa-miR-101: 002253; RNU6B: 001093) and TaqMan microRNA reverse transcription kit (Thermo Fisher Scientific) while miRNA expression was quantified on a 7500 Fast Real-time PCR instrument (Thermo Fisher Scientific) as earlier reported (10).…”

Section: Rna Isolation and Quantitative Real-time Pcrmentioning

confidence: 99%

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Prognostic relevance of proliferation-related miRNAs in pancreatic neuroendocrine neoplasms

Grolmusz

Kövesdi

Borka

et al. 2018

European Journal of Endocrinology

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Objective Pancreatic neuroendocrine neoplasms (PanNENs) are rare tumors arising from the endocrine pancreas, however their prognosis differs significantly upon their proliferative state which is characterized by histopathological grading. MiRNAs are small, noncoding RNAs posttranscriptionally regulating gene expression. Our aim was to identify miRNAs with altered expression upon proliferation which can be used as prognostic biomarkers in PanNENs. Methods MiRNA expression profiles of 40 PanNENs were downloaded from Gene Expression Omnibus and were reanalyzed upon tumor grades (discovery cohort). Results of the reanalysis were confirmed by qRT-PCR analysis of 5 miRNAs on an independent validation cohort of sixty three primary PanNEN samples. Cox proportional hazards survival regression model was fit for both univariate and multivariate analysis to determine the miRNAs' effect on progression-free and overall survival. Results 19 miRNAs displayed differential expression between tumor grades. The altered expression of 3 out of 5 chosen miRNAs was successfully validated; hsa-miR-21, hsa-miR-10a and hsa-miR-106b were up-regulated in more proliferative PanNENs compared to grade 1 tumors. In univariate analysis, higher expression of tissue hsa-miR-21, hsa-miR-10a and hsa-miR-106b expression of primary PanNENs predicted worse progression-free and overall survival, however multivariate analysis only confirmed the expression of hsa-miR-21 as an independent prognostic factor. Conclusions The expression of hsa-miR-106b, hsa-miR-10a and especially hsa-miR-21 has prognostic relevance regarding progression-free and overall survival in patients with PanNENs.

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“…Grolmusz et al [ 48 ] also investigated MEN1-targeting miRNAs as a possible underlying cause of menin deficiency in MEN1-associated and sporadic primary hyperparathyroidism (PHPT). Germinal MEN1 gene mutations were identified in all 14 patients; somatic MEN1 gene mutations were present in 25% of sporadic PHPTs tissues.…”

Section: Mirnas In Parathyroid Tumorsmentioning

confidence: 99%

Multiple Endocrine Neoplasia Type 1: The Potential Role of microRNAs in the Management of the Syndrome

Donati

Ciuffi²,

Marini³

et al. 2020

IJMS

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Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited tumor syndrome, characterized by the development of multiple neuroendocrine tumors (NETs) in a single patient. Major manifestations include primary hyperparathyroidism, gastro-entero-pancreatic neuroendocrine tumors, and pituitary adenomas. In addition to these main NETs, various combinations of more than 20 endocrine and non-endocrine tumors have been described in MEN1 patients. Despite advances in diagnostic techniques and treatment options, which are generally similar to those of sporadic tumors, patients with MEN1 have a poor life expectancy, and the need for targeted therapies is strongly felt. MEN1 is caused by germline heterozygous inactivating mutations of the MEN1 gene, which encodes menin, a tumor suppressor protein. The lack of a direct genotype–phenotype correlation does not permit the determination of the exact clinical course of the syndrome. One of the possible causes of this lack of association could be ascribed to epigenetic factors, including microRNAs (miRNAs), single-stranded non-coding small RNAs that negatively regulate post-transcriptional gene expression. Some miRNAs, and their deregulation, have been associated with MEN1 tumorigenesis. Recently, an extracellular class of miRNAs has also been identified (c-miRNAs); variations in their levels showed association with various human diseases, including tumors. The aim of this review is to provide a general overview on the involvement of miRNAs in MEN1 tumor development, to be used as possible targets for novel molecular therapies. The potential role of c-miRNAs as future non-invasive diagnostic and prognostic biomarkers of MEN1 will be discussed as well.

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MEN1 mutations and potentially MEN1-targeting miRNAs are responsible for menin deficiency in sporadic and MEN1 syndrome-associated primary hyperparathyroidism

Cited by 20 publications

References 40 publications

Differential expression of miRNA199b-5p as a novel biomarker for sporadic and hereditary parathyroid tumors

Differential expression of miRNA199b-5p as a novel biomarker for sporadic and hereditary parathyroid tumors

Prognostic relevance of proliferation-related miRNAs in pancreatic neuroendocrine neoplasms

Multiple Endocrine Neoplasia Type 1: The Potential Role of microRNAs in the Management of the Syndrome

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