Publication:
Epigenetic and post-transcriptional regulation of somatostatin receptor subtype 5 (SST5 ) in pituitary and pancreatic neuroendocrine tumors.

dc.contributor.authorPedraza-Arevalo, Sergio
dc.contributor.authorIbañez-Costa, Alejandro
dc.contributor.authorBlazquez-Encinas, Ricardo
dc.contributor.authorBranco, Miguel R
dc.contributor.authorVazquez-Borrego, Mari C
dc.contributor.authorHerrera-Martinez, Aura D
dc.contributor.authorVenegas-Moreno, Eva
dc.contributor.authorSerrano-Blanch, Raquel
dc.contributor.authorArjona-Sanchez, Alvaro
dc.contributor.authorGalvez-Moreno, Maria A
dc.contributor.authorKorbonits, Marta
dc.contributor.authorSoto-Moreno, Alfonso
dc.contributor.authorGahete, Manuel D
dc.contributor.authorCharalambous, Marika
dc.contributor.authorLuque, Raúl M
dc.contributor.authorCastaño, Justo P
dc.contributor.funderJunta de Andalucıa
dc.contributor.funderSpanish Ministry of Economy
dc.contributor.funderMinistry of Science and Innovation
dc.contributor.funderISCIII
dc.contributor.funderFEDER
dc.contributor.funderEuropean Union’s Seventh Framework Programme
dc.contributor.funderFundacion Eugenio Rodriguez Pascual
dc.contributor.funderUK Medical Research Council
dc.date.accessioned2023-05-03T15:09:25Z
dc.date.available2023-05-03T15:09:25Z
dc.date.issued2021-09-06
dc.description.abstractSomatostatin receptor subtype 5 (SST5 ) is an emerging biomarker and actionable target in pituitary (PitNETs) and pancreatic (PanNETs) neuroendocrine tumors. Transcriptional and epigenetic regulation of SSTR5 gene expression and mRNA biogenesis is poorly understood. Recently, an overlapping natural antisense transcript, SSTR5-AS1, potentially regulating SSTR5 expression, was identified. We aimed to elucidate whether epigenetic processes contribute to the regulation of SSTR5 expression in PitNETs (somatotropinomas) and PanNETs. We analyzed the SSTR5/SSTR5-AS1 human locus in silico to identify CpG islands. SSTR5 and SSTR5-AS1 expression was assessed by quantitative real-time PCR (qPCR) in 27 somatotropinomas, 11 normal pituitaries (NPs), and 15 PanNETs/paired adjacent (control) samples. We evaluated methylation grade in four CpG islands in the SSTR5/SSTR5-AS1 genes. Results revealed that SSTR5 and SSTR5-AS1 were directly correlated in NP, somatotropinoma, and PanNET samples. Interestingly, selected CpG islands were differentially methylated in somatotropinomas compared with NPs. In PanNETs cell lines, SSTR5-AS1 silencing downregulated SSTR5 expression, altered aggressiveness features, and influenced pasireotide response. These results provide evidence that SSTR5 expression in PitNETs and PanNETs can be epigenetically regulated by the SSTR5-AS1 antisense transcript and, indirectly, by DNA methylation, which may thereby impact tumor behavior and treatment response.
dc.description.sponsorshipThis research was funded by Junta de Andalucıa (BIO-0139, P20_00442; PEER-0048-2020); Spanish Ministry of Economy (BFU2016-80360-R), Ministry of Science and Innovation (PID2019-105201RB-I00, PID2019-105564RB-I00); and ISCIII (PI16-00264, CD19/00255), co-funded with EU funds from FEDER Program. People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under project WHRI-ACADEMY, (FPU14/04290, FPU18/02275); EMBO (short term fellowship 6802); GETNE G2019 Research Grant; Fundacion Eugenio Rodriguez Pascual (FERP2019); project grants from the UK Medical Research Council (MR/R022836/1; MR/L002345/1); and CIBERobn; CIBER Fisiopatología de la Obesidad y Nutrición is an initiative of Instituto de Salud Carlos III
dc.description.versionSi
dc.identifier.citationPedraza-Arevalo S, Ibáñez-Costa A, Blázquez-Encinas R, Branco MR, Vázquez-Borrego MC, Herrera-Martínez AD, et al. Epigenetic and post-transcriptional regulation of somatostatin receptor subtype 5 (SST5 ) in pituitary and pancreatic neuroendocrine tumors. Mol Oncol. 2022 Feb;16(3):764-779
dc.identifier.doi10.1002/1878-0261.13107
dc.identifier.essn1878-0261
dc.identifier.pmcPMC8807362
dc.identifier.pmid34601790
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807362/pdf
dc.identifier.unpaywallURLhttps://doi.org/10.1002/1878-0261.13107
dc.identifier.urihttp://hdl.handle.net/10668/22383
dc.issue.number3
dc.journal.titleMolecular oncology
dc.journal.titleabbreviationMol Oncol
dc.language.isoen
dc.organizationHospital Universitario Reina Sofía
dc.organizationInstituto Maimónides de Investigación Biomédica de Córdoba-IMIBIC
dc.organizationHospital Universitario Virgen del Rocío
dc.organizationInstituto de Biomedicina de Sevilla-IBIS
dc.page.number764-779
dc.provenanceRealizada la curación de contenido 07/04/2025
dc.publisherJohn Wiley & Sons
dc.pubmedtypeJournal Article
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.relation.projectIDBIO-0139
dc.relation.projectIDP20_00442
dc.relation.projectIDPEER-0048-2020
dc.relation.projectIDBFU2016-80360-R
dc.relation.projectIDPID2019-105201RB-I00
dc.relation.projectIDPID2019-105564RB-I00
dc.relation.projectIDPI16-00264
dc.relation.projectIDCD19/00255
dc.relation.projectIDFP7/2007-2013
dc.relation.projectID608765
dc.relation.projectIDFPU14/04290
dc.relation.projectIDFPU18/02275
dc.relation.projectIDFERP2019
dc.relation.projectIDR022836/1
dc.relation.projectIDMR/L002345/1
dc.relation.publisherversionhttps://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.13107
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectSST5
dc.subjectEpigenetics
dc.subjectNatural antisense transcript
dc.subjectNeuroendocrine tumors
dc.subjectPancreas
dc.subjectPituitary
dc.subject.decsEpigénesis genética
dc.subject.decsMetilación de ADN
dc.subject.decsNeoplasias hipofisarias
dc.subject.decsNeoplasias pancreáticas
dc.subject.decsReceptores de somatostatina
dc.subject.decsTumores neuroendocrinos
dc.subject.meshDNA methylation
dc.subject.meshEpigenesis, genetic
dc.subject.meshHumans
dc.subject.meshNeuroendocrine tumors
dc.subject.meshPancreatic neoplasms
dc.subject.meshPituitary neoplasms
dc.subject.meshReceptors, somatostatin
dc.titleEpigenetic and post-transcriptional regulation of somatostatin receptor subtype 5 (SST5 ) in pituitary and pancreatic neuroendocrine tumors.
dc.typeResearch article
dc.type.hasVersionVoR
dc.volume.number16
dspace.entity.typePublication

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