RT Journal Article
T1 Epigenetic and post-transcriptional regulation of somatostatin receptor subtype 5 (SST5 ) in pituitary and pancreatic neuroendocrine tumors.
A1 Pedraza-Arevalo, Sergio
A1 Ibáñez-Costa, Alejandro
A1 Blázquez-Encinas, Ricardo
A1 Branco, Miguel R
A1 Vázquez-Borrego, Mari C
A1 Herrera-Martínez, Aura D
A1 Venegas-Moreno, Eva
A1 Serrano-Blanch, Raquel
A1 Arjona-Sánchez, Álvaro
A1 Gálvez-Moreno, María A
A1 Korbonits, Marta
A1 Soto-Moreno, Alfonso
A1 Gahete, Manuel D
A1 Charalambous, Marika
A1 Luque, Raúl M
A1 Castaño, Justo P
K1 SST5
K1 epigenetics
K1 natural antisense transcript
K1 neuroendocrine tumors
K1 pancreas
K1 pituitary
AB 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.
YR 2021
FD 2021-10-26
LK https://hdl.handle.net/10668/25890
UL https://hdl.handle.net/10668/25890
LA en
DS RISalud
RD Apr 14, 2025