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A miR-129-5P/ARID3A Negative Feedback Loop Modulates Diffuse Large B Cell Lymphoma Progression and Immune Evasion Through Regulating the PD-1/PD-L1 Checkpoint

The activated B cell (ABC) and germinal center B cell (GCB) subtypes of diffuse large B cell lymphoma (DLBCL) have different gene expression profiles and clinical outcomes, and miRNAs have been reported to play important roles in tumorigenesis, progression, and metastasis. This study aimed to explor...

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Autores principales: Zheng, Weili, Lai, Guilan, Lin, Qiaochu, Issah, Mohammed Awal, Fu, Haiying, Shen, Jianzhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579866/
https://www.ncbi.nlm.nih.gov/pubmed/34778251
http://dx.doi.org/10.3389/fcell.2021.735855
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author Zheng, Weili
Lai, Guilan
Lin, Qiaochu
Issah, Mohammed Awal
Fu, Haiying
Shen, Jianzhen
author_facet Zheng, Weili
Lai, Guilan
Lin, Qiaochu
Issah, Mohammed Awal
Fu, Haiying
Shen, Jianzhen
author_sort Zheng, Weili
collection PubMed
description The activated B cell (ABC) and germinal center B cell (GCB) subtypes of diffuse large B cell lymphoma (DLBCL) have different gene expression profiles and clinical outcomes, and miRNAs have been reported to play important roles in tumorigenesis, progression, and metastasis. This study aimed to explore the differentially expressed miRNAs and target genes in the two main subtypes of DLBCL. Hub miRNAs were identified by constructing a regulatory network, and in vitro experiments and peripheral blood samples of DLBCL were used to explore the functions and mechanisms of differential miRNAs and mRNAs. Differentially expressed miRNAs and genes associated with the two DLBCL subtypes were identified using GEO datasets. Weighted gene co-expression network analysis shows that one gene module was associated with a better prognosis of patients with the GCB subtype. Through the construction of a regulatory network and qPCR verification of clinical samples and cell lines, miR-129-5p was identified as an important differential miRNA between the ABC and GCB subtypes. The negative relationship between miR-129-5p and ARID3A in DLBCL was confirmed using luciferase reporter assays. Overexpression of miR-129-5p and knockdown of ARID3A inhibited the proliferation of SU-DHL-2 (ABC-type) cells and promoted their apoptosis through the JAK and STAT6 signaling pathways. In addition, inhibition of miR-129-5p and overexpression of ARID3A promoted the proliferation and reduced apoptosis of DB and SU-DHL-6 (GCB-type) cells. Inhibition of miR-129-5p and overexpression of ARID3A in DB and SU-DHL-6 promoted immune escape by increasing PD-L1 expression, which was transcriptionally activated by ARID3A. In conclusion, we showed for the first time that the mir-129-5P/ARID3A negative feedback loop modulates DLBCL progression and immune evasion by regulating PD-1/PD-L1.
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spelling pubmed-85798662021-11-11 A miR-129-5P/ARID3A Negative Feedback Loop Modulates Diffuse Large B Cell Lymphoma Progression and Immune Evasion Through Regulating the PD-1/PD-L1 Checkpoint Zheng, Weili Lai, Guilan Lin, Qiaochu Issah, Mohammed Awal Fu, Haiying Shen, Jianzhen Front Cell Dev Biol Cell and Developmental Biology The activated B cell (ABC) and germinal center B cell (GCB) subtypes of diffuse large B cell lymphoma (DLBCL) have different gene expression profiles and clinical outcomes, and miRNAs have been reported to play important roles in tumorigenesis, progression, and metastasis. This study aimed to explore the differentially expressed miRNAs and target genes in the two main subtypes of DLBCL. Hub miRNAs were identified by constructing a regulatory network, and in vitro experiments and peripheral blood samples of DLBCL were used to explore the functions and mechanisms of differential miRNAs and mRNAs. Differentially expressed miRNAs and genes associated with the two DLBCL subtypes were identified using GEO datasets. Weighted gene co-expression network analysis shows that one gene module was associated with a better prognosis of patients with the GCB subtype. Through the construction of a regulatory network and qPCR verification of clinical samples and cell lines, miR-129-5p was identified as an important differential miRNA between the ABC and GCB subtypes. The negative relationship between miR-129-5p and ARID3A in DLBCL was confirmed using luciferase reporter assays. Overexpression of miR-129-5p and knockdown of ARID3A inhibited the proliferation of SU-DHL-2 (ABC-type) cells and promoted their apoptosis through the JAK and STAT6 signaling pathways. In addition, inhibition of miR-129-5p and overexpression of ARID3A promoted the proliferation and reduced apoptosis of DB and SU-DHL-6 (GCB-type) cells. Inhibition of miR-129-5p and overexpression of ARID3A in DB and SU-DHL-6 promoted immune escape by increasing PD-L1 expression, which was transcriptionally activated by ARID3A. In conclusion, we showed for the first time that the mir-129-5P/ARID3A negative feedback loop modulates DLBCL progression and immune evasion by regulating PD-1/PD-L1. Frontiers Media S.A. 2021-10-27 /pmc/articles/PMC8579866/ /pubmed/34778251 http://dx.doi.org/10.3389/fcell.2021.735855 Text en Copyright © 2021 Zheng, Lai, Lin, Issah, Fu and Shen. https://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 Cell and Developmental Biology
Zheng, Weili
Lai, Guilan
Lin, Qiaochu
Issah, Mohammed Awal
Fu, Haiying
Shen, Jianzhen
A miR-129-5P/ARID3A Negative Feedback Loop Modulates Diffuse Large B Cell Lymphoma Progression and Immune Evasion Through Regulating the PD-1/PD-L1 Checkpoint
title A miR-129-5P/ARID3A Negative Feedback Loop Modulates Diffuse Large B Cell Lymphoma Progression and Immune Evasion Through Regulating the PD-1/PD-L1 Checkpoint
title_full A miR-129-5P/ARID3A Negative Feedback Loop Modulates Diffuse Large B Cell Lymphoma Progression and Immune Evasion Through Regulating the PD-1/PD-L1 Checkpoint
title_fullStr A miR-129-5P/ARID3A Negative Feedback Loop Modulates Diffuse Large B Cell Lymphoma Progression and Immune Evasion Through Regulating the PD-1/PD-L1 Checkpoint
title_full_unstemmed A miR-129-5P/ARID3A Negative Feedback Loop Modulates Diffuse Large B Cell Lymphoma Progression and Immune Evasion Through Regulating the PD-1/PD-L1 Checkpoint
title_short A miR-129-5P/ARID3A Negative Feedback Loop Modulates Diffuse Large B Cell Lymphoma Progression and Immune Evasion Through Regulating the PD-1/PD-L1 Checkpoint
title_sort mir-129-5p/arid3a negative feedback loop modulates diffuse large b cell lymphoma progression and immune evasion through regulating the pd-1/pd-l1 checkpoint
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579866/
https://www.ncbi.nlm.nih.gov/pubmed/34778251
http://dx.doi.org/10.3389/fcell.2021.735855
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