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Role of miR200b-5p miRNA in lymphomagenesis associated with Sjögren’s syndrome (SS)

BACKGROUND: Development of non-Hodgkin’s lymphoma (NHL) is the major adverse outcome of primary Sjögren’s Syndrome (pSS) affecting both morbidity and mortality. The high frequency of transformation to lymphoid malignancy in pSS among autoimmune rheumatic diseases (6–10% of patients) and the accessib...

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Autores principales: Kapsogeorgou, Efstathia K., Tzioufas, Athanasios G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Mediterranean Journal of Rheumatology (MJR) 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045955/
https://www.ncbi.nlm.nih.gov/pubmed/32185300
http://dx.doi.org/10.31138/mjr.29.1.56
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author Kapsogeorgou, Efstathia K.
Tzioufas, Athanasios G.
author_facet Kapsogeorgou, Efstathia K.
Tzioufas, Athanasios G.
author_sort Kapsogeorgou, Efstathia K.
collection PubMed
description BACKGROUND: Development of non-Hodgkin’s lymphoma (NHL) is the major adverse outcome of primary Sjögren’s Syndrome (pSS) affecting both morbidity and mortality. The high frequency of transformation to lymphoid malignancy in pSS among autoimmune rheumatic diseases (6–10% of patients) and the accessibility of the affected organ (minor salivary glands; MSG), render pSS an ideal model for the study of lymphomagenesis associated with autoimmune diseases and inflammation. Although pSS-related lymphoid transformation is generally considered as an antigen-driven, multi-step process owed to the chronic activation of B-cells in MSGs, the underlying mechanisms remain elusive. Our recent results support that miR200b-5p miRNA is significantly down-regulated in the MSGs of pSS patients who have or will develop lymphoma, long before lymphoma clinical onset, indicating that it may be involved in lymphomagenesis. AIM: To investigate the role of miR200b-5p miRNA in pSS-associated lymphomagenesis. METHODS: At first, the miR200b-5p-expression will be examined by in situ hybridization in MSGs of pSS patients who are at low risk and have not developed NHL during follow-up, high risk and developed NHL in the future (pre-lymphoma) or have NHL, and the expressing cellular types, as well as those with reduced expression during lymphomagenesis, will be identified. Then, the miR200b-5p targeted molecular pathways in those cellular types (epithelial, B-cells and/or other lymphocytes, all non-neoplastic) will be studied in in vitro experiments by over-expressing and silencing of miR200b-5p, followed by transcriptome analysis. This approach is expected to find possibly novel pathogenetic mechanisms underlying SS-related lymphomagenesis. The latter is of high significance, not only for the understanding of lymphomagenesis, but also for its reversal and/or treatment. ANTICIPATED BENEFITS: This approach is anticipated to a) reveal the differentially regulated molecules and pathways by miR200b-5p, b) enlighten novel pathogenetic pathways underlying lymphomagenesis and c) identify novel therapeutic targets and possibly evidence-based therapeutic interventions.
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spelling pubmed-70459552020-03-17 Role of miR200b-5p miRNA in lymphomagenesis associated with Sjögren’s syndrome (SS) Kapsogeorgou, Efstathia K. Tzioufas, Athanasios G. Mediterr J Rheumatol Research Protocols-Proposals BACKGROUND: Development of non-Hodgkin’s lymphoma (NHL) is the major adverse outcome of primary Sjögren’s Syndrome (pSS) affecting both morbidity and mortality. The high frequency of transformation to lymphoid malignancy in pSS among autoimmune rheumatic diseases (6–10% of patients) and the accessibility of the affected organ (minor salivary glands; MSG), render pSS an ideal model for the study of lymphomagenesis associated with autoimmune diseases and inflammation. Although pSS-related lymphoid transformation is generally considered as an antigen-driven, multi-step process owed to the chronic activation of B-cells in MSGs, the underlying mechanisms remain elusive. Our recent results support that miR200b-5p miRNA is significantly down-regulated in the MSGs of pSS patients who have or will develop lymphoma, long before lymphoma clinical onset, indicating that it may be involved in lymphomagenesis. AIM: To investigate the role of miR200b-5p miRNA in pSS-associated lymphomagenesis. METHODS: At first, the miR200b-5p-expression will be examined by in situ hybridization in MSGs of pSS patients who are at low risk and have not developed NHL during follow-up, high risk and developed NHL in the future (pre-lymphoma) or have NHL, and the expressing cellular types, as well as those with reduced expression during lymphomagenesis, will be identified. Then, the miR200b-5p targeted molecular pathways in those cellular types (epithelial, B-cells and/or other lymphocytes, all non-neoplastic) will be studied in in vitro experiments by over-expressing and silencing of miR200b-5p, followed by transcriptome analysis. This approach is expected to find possibly novel pathogenetic mechanisms underlying SS-related lymphomagenesis. The latter is of high significance, not only for the understanding of lymphomagenesis, but also for its reversal and/or treatment. ANTICIPATED BENEFITS: This approach is anticipated to a) reveal the differentially regulated molecules and pathways by miR200b-5p, b) enlighten novel pathogenetic pathways underlying lymphomagenesis and c) identify novel therapeutic targets and possibly evidence-based therapeutic interventions. The Mediterranean Journal of Rheumatology (MJR) 2018-03-19 /pmc/articles/PMC7045955/ /pubmed/32185300 http://dx.doi.org/10.31138/mjr.29.1.56 Text en © 2018 The Mediterranean Journal of Rheumatology (MJR) http://creativecommons.org/licenses/by/4.0/ This work is licensed under and Creative Commons Attribution-NonCommercial 4.0 International License.
spellingShingle Research Protocols-Proposals
Kapsogeorgou, Efstathia K.
Tzioufas, Athanasios G.
Role of miR200b-5p miRNA in lymphomagenesis associated with Sjögren’s syndrome (SS)
title Role of miR200b-5p miRNA in lymphomagenesis associated with Sjögren’s syndrome (SS)
title_full Role of miR200b-5p miRNA in lymphomagenesis associated with Sjögren’s syndrome (SS)
title_fullStr Role of miR200b-5p miRNA in lymphomagenesis associated with Sjögren’s syndrome (SS)
title_full_unstemmed Role of miR200b-5p miRNA in lymphomagenesis associated with Sjögren’s syndrome (SS)
title_short Role of miR200b-5p miRNA in lymphomagenesis associated with Sjögren’s syndrome (SS)
title_sort role of mir200b-5p mirna in lymphomagenesis associated with sjögren’s syndrome (ss)
topic Research Protocols-Proposals
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045955/
https://www.ncbi.nlm.nih.gov/pubmed/32185300
http://dx.doi.org/10.31138/mjr.29.1.56
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