Evidence map›Paper›PMID 39607643›Full record

ArticleEndocrine2025

Aberrant promoter methylation, expression and function of RASSF1A gene in a series of Italian parathyroid tumors.

Chiara Verdelli, Federico Pio Fabrizio, Paola Maroni, Annamaria Morotti, Giulia Stefania Tavanti, Silvia Carrara, Vito Guarnieri, Filomena Cetani, Alfredo Scillitani, Riccardo Maggiore and 4 more

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Article in Endocrine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

What it found

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

14 authors.

Chiara VerdelliLaboratory of Experimental Biochemistry and Molecular Biology, IRCCS Ospedale Galeazzi-Sant'Ambrogio, Milan, Italy.
Federico Pio FabrizioLaboratory of Oncology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
Paola MaroniLaboratory of Experimental Biochemistry and Molecular Biology, IRCCS Ospedale Galeazzi-Sant'Ambrogio, Milan, Italy.
Annamaria MorottiDivision of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Giulia Stefania TavantiLaboratory of Experimental Biochemistry and Molecular Biology, IRCCS Ospedale Galeazzi-Sant'Ambrogio, Milan, Italy.
Silvia CarraraDepartment of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
Vito GuarnieriDivision of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
Filomena CetaniDepartment of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Pisa, Italy.
Alfredo ScillitaniEndocrine Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
Riccardo MaggioreEndocrine Surgery, IRCCS Ospedale San Raffaele, Milan, Italy.
Francesca PerticoneEndocrine Unit, IRCCS Ospedale San Raffaele, Milan, Italy.
Valentina VairaDivision of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Lucia Anna MuscarellaLaboratory of Oncology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
Sabrina CorbettaDepartment of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy. sabrina.corbetta@unimi.it.ORCID 0000-0001-8140-3175

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeAberrant epigenetic features are key events involved in parathyroid tumorigenesis, including DNA methylation, histone methylation, and non-coding RNAs. Ras Association Domain Family Protein1 Isoform A (RASSF1A) and Adenomatous Polyposis of Colon (APC) are frequently downregulated in human cancers. Here, we investigated their deregulated expression and the potential role in parathyroid neoplasms.

methodsmethylation of RASSF1A and APC promoters was analyzed in a series of parathyroid adenomas (PAds, n = 80) and parathyroid carcinomas (PCas, n = 9) from Italian patients with primary hyperparathyroidism,

resultsRASSF1A and APC promoter methylation occurred in about 90% of PAds samples. PCas displayed RASSF1A promoter methylation, while APC promoter was methylated only in 2 samples. Of note, RASSF1A promoter methylation negatively correlated with PAds tumor size. However, RASSF1A transcript and protein levels were reduced in PAds and PCas compared with parathyroid normal glands. Investigating the potential mechanism involved in RASSF1A promoter methylation, we found that DNA methyltransferases (DNMTs) activity was variable in PAds and inversely correlated with RASSF1A protein levels. In addition, the RASSF1A promoter methylation negatively correlated with long-non-coding Antisense Intronic Noncoding RASSF1A (ANRASSF1A) mRNA levels, excluding the involvement of ANRASSF1 in RASSF1A regulation. In HEK293A cells transfected with the calcium sensing receptor (CASR), loss of RASSF1A increased basal phosphorylated Extracellular signal-regulated kinase (pERK/ERK) levels blunting the CASR-induced increases.

conclusionRASSF1A and APC promoter methylation is a hallmark of parathyroid tumors; deregulation of DNMTs activity contributes to modulation of RASSF1A expression. Loss of RASSF1A may be involved in the tuning of ERK pathway in parathyroid tumors.

Indexed as

AdenomaDNA MethylationParathyroid NeoplasmsPromoter Regions, GeneticTumor Suppressor ProteinsAdenomatous Polyposis Coli ProteinAdultAgedFemaleGene Expression Regulation, NeoplasticHumansItalyMaleMiddle AgedAdenomatous Polyposis Coli ProteinRASSF1 protein, humanTumor Suppressor ProteinsAPCDNA MethylationDNMTsparathyroid tumorsPTHRASSF1

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.