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© 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Somatostatin 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.

Details

Title
Epigenetic and post‐transcriptional regulation of somatostatin receptor subtype 5 (SST5) in pituitary and pancreatic neuroendocrine tumors
Author
Sergio Pedraza‐Arevalo 1 ; Alejandro Ibáñez‐Costa 1   VIAFID ORCID Logo  ; Ricardo Blázquez‐Encinas 1 ; Branco, Miguel R 2 ; Mari C. Vázquez‐Borrego 1 ; Aura D. Herrera‐Martínez 3 ; Eva Venegas‐Moreno 4 ; Raquel Serrano‐Blanch 5 ; Álvaro Arjona‐Sánchez 6 ; María A. Gálvez‐Moreno 3 ; Korbonits, Marta 7 ; Alfonso Soto‐Moreno 4 ; Gahete, Manuel D 1   VIAFID ORCID Logo  ; Charalambous, Marika 8 ; Luque, Raúl M 1 ; Castaño, Justo P 1   VIAFID ORCID Logo 

 Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain; Reina Sofia University Hospital, Córdoba, Spain 
 Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK 
 Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain; Endocrinology and Nutrition Service, Reina Sofia University Hospital, Córdoba, Spain 
 Metabolism and Nutrition Unit, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain 
 Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain; Medical Oncology Service, Reina Sofia University Hospital, Córdoba, Spain 
 Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain; Surgery Service, Reina Sofia University Hospital, Córdoba, Spain 
 Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK 
 Developmental Epigenetics group, Department of Medical and Molecular Genetics, King’s College of London, London, UK 
Pages
764-779
Section
Research Articles
Publication year
2022
Publication date
Feb 2022
Publisher
John Wiley & Sons, Inc.
ISSN
15747891
e-ISSN
18780261
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2624576474
Copyright
© 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.