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Evaluation of the expression of necroptosis pathway mediators and its association with tumor characteristics in functional and non-functional pituitary adenomas

BACKGROUND: Pituitary adenomas impose a burden of morbidity on patients and characterizing the molecular mechanisms underlying its pathogenesis received remarkable attention. Despite the appealing role of necroptosis as an alternative cell death pathway in cancer pathogenesis, its relevance to pitui...

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Autores principales: Khamseh, Mohammad E., Sheikhi, Alireza, Shahsavari, Zahra, Ghorbani, Mohammad, Akbari, Hamideh, Imani, Mehrnaz, Panahi, Mahshid, Alimohammadi, Alimohammad, Ameri, Maryam, Nazem, Shima, Salimi, Vahid, Tavakoli-Yaraki, Masoumeh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725329/
https://www.ncbi.nlm.nih.gov/pubmed/34983494
http://dx.doi.org/10.1186/s12902-021-00919-y
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author Khamseh, Mohammad E.
Sheikhi, Alireza
Shahsavari, Zahra
Ghorbani, Mohammad
Akbari, Hamideh
Imani, Mehrnaz
Panahi, Mahshid
Alimohammadi, Alimohammad
Ameri, Maryam
Nazem, Shima
Salimi, Vahid
Tavakoli-Yaraki, Masoumeh
author_facet Khamseh, Mohammad E.
Sheikhi, Alireza
Shahsavari, Zahra
Ghorbani, Mohammad
Akbari, Hamideh
Imani, Mehrnaz
Panahi, Mahshid
Alimohammadi, Alimohammad
Ameri, Maryam
Nazem, Shima
Salimi, Vahid
Tavakoli-Yaraki, Masoumeh
author_sort Khamseh, Mohammad E.
collection PubMed
description BACKGROUND: Pituitary adenomas impose a burden of morbidity on patients and characterizing the molecular mechanisms underlying its pathogenesis received remarkable attention. Despite the appealing role of necroptosis as an alternative cell death pathway in cancer pathogenesis, its relevance to pituitary adenoma pathogenesis has yet to be determined that is perused in the current study. METHODS: The total number of 109 specimens including pituitary adenomas and cadaveric healthy pituitary tissues were enrolled in the current study. Tumor and healthy pituitary tissues were subjected to RNA extraction and gene analysis using Real-Time PCR. The expression levels of necroptosis markers (RIP1K, RIP3K and, MLKL) and their association with the patient’s demographic features were evaluated, also the protein level of MLKL was assessed using immunohistochemistry in tissues. RESULTS: Based on our data, the remarkable reduction in RIP3K and MLKL expression were detected in nonfunctional and GH-secreting pituitary tumors compared to pituitary normal tissues. Invasive tumors revealed lower expression of RIP3K and MLKL compared to non-invasive tumors, also the attenuated level of MLKL was associated with the tumor size in invasive NFPA. The simultaneous down-regulation of MLKL protein in pituitary adenoma tissues was observed which was in line with its gene expression. While, RIP1K over-expressed significantly in both types of pituitary tumors which showed no significant correlation with patient’s age, gender and tumor size in GHPPA and NFPA group. Notably, MLKL and RIP3K gene expression was significantly correlated in the GHPPA group. CONCLUSIONS: According to our data, the reduced expression of necroptosis mediators (RIP3K, MLKL) in pituitary adenoma reinforces the hypothesis that the necroptosis pathway can be effective in regulating the proliferation and growth of pituitary tumor cells and tumor recurrence.
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spelling pubmed-87253292022-01-06 Evaluation of the expression of necroptosis pathway mediators and its association with tumor characteristics in functional and non-functional pituitary adenomas Khamseh, Mohammad E. Sheikhi, Alireza Shahsavari, Zahra Ghorbani, Mohammad Akbari, Hamideh Imani, Mehrnaz Panahi, Mahshid Alimohammadi, Alimohammad Ameri, Maryam Nazem, Shima Salimi, Vahid Tavakoli-Yaraki, Masoumeh BMC Endocr Disord Research BACKGROUND: Pituitary adenomas impose a burden of morbidity on patients and characterizing the molecular mechanisms underlying its pathogenesis received remarkable attention. Despite the appealing role of necroptosis as an alternative cell death pathway in cancer pathogenesis, its relevance to pituitary adenoma pathogenesis has yet to be determined that is perused in the current study. METHODS: The total number of 109 specimens including pituitary adenomas and cadaveric healthy pituitary tissues were enrolled in the current study. Tumor and healthy pituitary tissues were subjected to RNA extraction and gene analysis using Real-Time PCR. The expression levels of necroptosis markers (RIP1K, RIP3K and, MLKL) and their association with the patient’s demographic features were evaluated, also the protein level of MLKL was assessed using immunohistochemistry in tissues. RESULTS: Based on our data, the remarkable reduction in RIP3K and MLKL expression were detected in nonfunctional and GH-secreting pituitary tumors compared to pituitary normal tissues. Invasive tumors revealed lower expression of RIP3K and MLKL compared to non-invasive tumors, also the attenuated level of MLKL was associated with the tumor size in invasive NFPA. The simultaneous down-regulation of MLKL protein in pituitary adenoma tissues was observed which was in line with its gene expression. While, RIP1K over-expressed significantly in both types of pituitary tumors which showed no significant correlation with patient’s age, gender and tumor size in GHPPA and NFPA group. Notably, MLKL and RIP3K gene expression was significantly correlated in the GHPPA group. CONCLUSIONS: According to our data, the reduced expression of necroptosis mediators (RIP3K, MLKL) in pituitary adenoma reinforces the hypothesis that the necroptosis pathway can be effective in regulating the proliferation and growth of pituitary tumor cells and tumor recurrence. BioMed Central 2022-01-04 /pmc/articles/PMC8725329/ /pubmed/34983494 http://dx.doi.org/10.1186/s12902-021-00919-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Khamseh, Mohammad E.
Sheikhi, Alireza
Shahsavari, Zahra
Ghorbani, Mohammad
Akbari, Hamideh
Imani, Mehrnaz
Panahi, Mahshid
Alimohammadi, Alimohammad
Ameri, Maryam
Nazem, Shima
Salimi, Vahid
Tavakoli-Yaraki, Masoumeh
Evaluation of the expression of necroptosis pathway mediators and its association with tumor characteristics in functional and non-functional pituitary adenomas
title Evaluation of the expression of necroptosis pathway mediators and its association with tumor characteristics in functional and non-functional pituitary adenomas
title_full Evaluation of the expression of necroptosis pathway mediators and its association with tumor characteristics in functional and non-functional pituitary adenomas
title_fullStr Evaluation of the expression of necroptosis pathway mediators and its association with tumor characteristics in functional and non-functional pituitary adenomas
title_full_unstemmed Evaluation of the expression of necroptosis pathway mediators and its association with tumor characteristics in functional and non-functional pituitary adenomas
title_short Evaluation of the expression of necroptosis pathway mediators and its association with tumor characteristics in functional and non-functional pituitary adenomas
title_sort evaluation of the expression of necroptosis pathway mediators and its association with tumor characteristics in functional and non-functional pituitary adenomas
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725329/
https://www.ncbi.nlm.nih.gov/pubmed/34983494
http://dx.doi.org/10.1186/s12902-021-00919-y
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