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Medication for Acromegaly Reduces Expression of MUC16, MACC1 and GRHL2 in Pituitary Neuroendocrine Tumour Tissue

Acromegaly is a disease mainly caused by pituitary neuroendocrine tumor (PitNET) overproducing growth hormone. First-line medication for this condition is the use of somatostatin analogs (SSAs), that decrease tumor mass and induce antiproliferative effects on PitNET cells. Dopamine agonists (DAs) ca...

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Autores principales: Saksis, Rihards, Silamikelis, Ivars, Laksa, Pola, Megnis, Kaspars, Peculis, Raitis, Mandrika, Ilona, Rogoza, Olesja, Petrovska, Ramona, Balcere, Inga, Konrade, Ilze, Steina, Liva, Stukens, Janis, Breiksa, Austra, Nazarovs, Jurijs, Sokolovska, Jelizaveta, Pirags, Valdis, Klovins, Janis, Rovite, Vita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928352/
https://www.ncbi.nlm.nih.gov/pubmed/33680922
http://dx.doi.org/10.3389/fonc.2020.593760
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author Saksis, Rihards
Silamikelis, Ivars
Laksa, Pola
Megnis, Kaspars
Peculis, Raitis
Mandrika, Ilona
Rogoza, Olesja
Petrovska, Ramona
Balcere, Inga
Konrade, Ilze
Steina, Liva
Stukens, Janis
Breiksa, Austra
Nazarovs, Jurijs
Sokolovska, Jelizaveta
Pirags, Valdis
Klovins, Janis
Rovite, Vita
author_facet Saksis, Rihards
Silamikelis, Ivars
Laksa, Pola
Megnis, Kaspars
Peculis, Raitis
Mandrika, Ilona
Rogoza, Olesja
Petrovska, Ramona
Balcere, Inga
Konrade, Ilze
Steina, Liva
Stukens, Janis
Breiksa, Austra
Nazarovs, Jurijs
Sokolovska, Jelizaveta
Pirags, Valdis
Klovins, Janis
Rovite, Vita
author_sort Saksis, Rihards
collection PubMed
description Acromegaly is a disease mainly caused by pituitary neuroendocrine tumor (PitNET) overproducing growth hormone. First-line medication for this condition is the use of somatostatin analogs (SSAs), that decrease tumor mass and induce antiproliferative effects on PitNET cells. Dopamine agonists (DAs) can also be used if SSA treatment is not effective. This study aimed to determine differences in transcriptome signatures induced by SSA/DA therapy in PitNET tissue. We selected tumor tissue from twelve patients with somatotropinomas, with half of the patients receiving SSA/DA treatment before surgery and the other half treatment naive. Transcriptome sequencing was then carried out to identify differentially expressed genes (DEGs) and their protein–protein interactions, using pathway analyses. We found 34 upregulated and six downregulated DEGs in patients with SSA/DA treatment. Three tumor development promoting factors MUC16, MACC1, and GRHL2, were significantly downregulated in therapy administered PitNET tissue; this finding was supported by functional studies in GH3 cells. Protein–protein interactions and pathway analyses revealed extracellular matrix involvement in the antiproliferative effects of this type of the drug treatment, with pronounced alterations in collagen regulation. Here, we have demonstrated that somatotropinomas can be distinguished based on their transcriptional profiles following SSA/DA therapy, and SSA/DA treatment does indeed cause changes in gene expression. Treatment with SSA/DA significantly downregulated several factors involved in tumorigenesis, including MUC16, MACC1, and GRHL2. Genes that were upregulated, however, did not have a direct influence on antiproliferative function in the PitNET cells. These findings suggested that SSA/DA treatment acted in a tumor suppressive manner and furthermore, collagen related interactions and pathways were enriched, implicating extracellular matrix involvement in this anti-tumor effect of drug treatment.
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spelling pubmed-79283522021-03-04 Medication for Acromegaly Reduces Expression of MUC16, MACC1 and GRHL2 in Pituitary Neuroendocrine Tumour Tissue Saksis, Rihards Silamikelis, Ivars Laksa, Pola Megnis, Kaspars Peculis, Raitis Mandrika, Ilona Rogoza, Olesja Petrovska, Ramona Balcere, Inga Konrade, Ilze Steina, Liva Stukens, Janis Breiksa, Austra Nazarovs, Jurijs Sokolovska, Jelizaveta Pirags, Valdis Klovins, Janis Rovite, Vita Front Oncol Oncology Acromegaly is a disease mainly caused by pituitary neuroendocrine tumor (PitNET) overproducing growth hormone. First-line medication for this condition is the use of somatostatin analogs (SSAs), that decrease tumor mass and induce antiproliferative effects on PitNET cells. Dopamine agonists (DAs) can also be used if SSA treatment is not effective. This study aimed to determine differences in transcriptome signatures induced by SSA/DA therapy in PitNET tissue. We selected tumor tissue from twelve patients with somatotropinomas, with half of the patients receiving SSA/DA treatment before surgery and the other half treatment naive. Transcriptome sequencing was then carried out to identify differentially expressed genes (DEGs) and their protein–protein interactions, using pathway analyses. We found 34 upregulated and six downregulated DEGs in patients with SSA/DA treatment. Three tumor development promoting factors MUC16, MACC1, and GRHL2, were significantly downregulated in therapy administered PitNET tissue; this finding was supported by functional studies in GH3 cells. Protein–protein interactions and pathway analyses revealed extracellular matrix involvement in the antiproliferative effects of this type of the drug treatment, with pronounced alterations in collagen regulation. Here, we have demonstrated that somatotropinomas can be distinguished based on their transcriptional profiles following SSA/DA therapy, and SSA/DA treatment does indeed cause changes in gene expression. Treatment with SSA/DA significantly downregulated several factors involved in tumorigenesis, including MUC16, MACC1, and GRHL2. Genes that were upregulated, however, did not have a direct influence on antiproliferative function in the PitNET cells. These findings suggested that SSA/DA treatment acted in a tumor suppressive manner and furthermore, collagen related interactions and pathways were enriched, implicating extracellular matrix involvement in this anti-tumor effect of drug treatment. Frontiers Media S.A. 2021-02-15 /pmc/articles/PMC7928352/ /pubmed/33680922 http://dx.doi.org/10.3389/fonc.2020.593760 Text en Copyright © 2021 Saksis, Silamikelis, Laksa, Megnis, Peculis, Mandrika, Rogoza, Petrovska, Balcere, Konrade, Steina, Stukens, Breiksa, Nazarovs, Sokolovska, Pirags, Klovins and Rovite http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Saksis, Rihards
Silamikelis, Ivars
Laksa, Pola
Megnis, Kaspars
Peculis, Raitis
Mandrika, Ilona
Rogoza, Olesja
Petrovska, Ramona
Balcere, Inga
Konrade, Ilze
Steina, Liva
Stukens, Janis
Breiksa, Austra
Nazarovs, Jurijs
Sokolovska, Jelizaveta
Pirags, Valdis
Klovins, Janis
Rovite, Vita
Medication for Acromegaly Reduces Expression of MUC16, MACC1 and GRHL2 in Pituitary Neuroendocrine Tumour Tissue
title Medication for Acromegaly Reduces Expression of MUC16, MACC1 and GRHL2 in Pituitary Neuroendocrine Tumour Tissue
title_full Medication for Acromegaly Reduces Expression of MUC16, MACC1 and GRHL2 in Pituitary Neuroendocrine Tumour Tissue
title_fullStr Medication for Acromegaly Reduces Expression of MUC16, MACC1 and GRHL2 in Pituitary Neuroendocrine Tumour Tissue
title_full_unstemmed Medication for Acromegaly Reduces Expression of MUC16, MACC1 and GRHL2 in Pituitary Neuroendocrine Tumour Tissue
title_short Medication for Acromegaly Reduces Expression of MUC16, MACC1 and GRHL2 in Pituitary Neuroendocrine Tumour Tissue
title_sort medication for acromegaly reduces expression of muc16, macc1 and grhl2 in pituitary neuroendocrine tumour tissue
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928352/
https://www.ncbi.nlm.nih.gov/pubmed/33680922
http://dx.doi.org/10.3389/fonc.2020.593760
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