PAX5 interacts with RIP2 to promote NF-κB activation and drug-resistance of B-lymphoproliferative disorders

Wang, Dong; Chen, Jingyu; Li, Rui; Wu, Guolin; Sun, Zimin; Wang, Zhitao; Zhai, Zhimin; Fang, Fang; Guo, Yugang; Zhong, Yaohua; Jiang, Ming; Xu, Huan; Chen, Minhua; Shen, Guodong; Sun, Jie; Yan, Bailing; Yu, Chundong; Tian, Zhigang; Xiao, Weihua

doi:10.1242/jcs.183889

Cited by 10 publications

(17 citation statements)

References 47 publications

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“…3 b). Moreover, it is noting that cisplatin resistance by the high expression of IKKα and further affecting up-regulation expression of NF-κB, not IKKβ which IKKβ is considered as classic path way to activate NF-κB [ 16 ].…”

Section: Resultsmentioning

confidence: 99%

ETS1 is associated with cisplatin resistance through IKKα/NF-κB pathway in cell line MDA-MB-231

Zhang

et al. 2018

Cancer Cell Int

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BackgroundPlatinum-based drugs are used extensively in neoadjuvant chemotherapy for triple-negative breast cancer (TNBC), but their use can be limited by resistance. In this study, we established cisplatin (DDP) resistant TNBC cells to investigate the potential relationship among ETS1, IKKα/NF-κB and resistance.MethodsThe sensitivity was evaluated by MTT, apoptosis analysis. The intracellular DDP concentration difference was tested by inductively coupled plasma mass spectrometry (ICP-MS) method. Molecular pathological mechanism of DDP resistance was explored by microarray analysis and PPI network analysis. The ETS1, NF-κB signaling change were assessed by western blot and q-PCR in vitro and vivo. The existing binds between ETS1 and the core IKKα promoter were found by luciferase assay and chromatin immunoprecipitation technique (ChIP).ResultsMDA-MB-231/DDP (231/DDP) cell had a higher IC50 value of cisplatin, lower intracellular DDP concentration, and lower apoptosis ratio than MDA-MB-231 (231/wt) cell line treated with DDP. Increased ABC transporters were induced by the activation of NF-κB pathway in 231/DDP cells. ETS1, RPL6, RBBP8, BIRC2, PIK3A and RARS were six important genes for DDP-resistance based on PPI network and expression validation. Protein expression of ETS1 and IKKα were significantly up-regulated in 231/DDP cells. However, inhibition of ETS1 expression enhances chemo-sensitivity to DDP and reversed the activation of NF-κB pathway in 231/DDP cells and subcutaneous transplantation tumor in vivo. Moreover, there is existing binds between ETS1 and the core IKKα promoter though luciferase assay and ChIP.ConclusionThis study enables us to understand the functions of ETS1 in TNBC chemotherapy and suggests that ETS1 could be used as a novel marker of poor response to DDP and a potential therapeutic target for TNBC chemotherapy.

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Section: Resultsmentioning

confidence: 99%

ETS1 is associated with cisplatin resistance through IKKα/NF-κB pathway in cell line MDA-MB-231

Zhang

et al. 2018

Cancer Cell Int

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“…Real et al proposed that upregulation of CCND2 is involved in the protection against Gamma‐secretase inhibitors (GSIs), which are Notch pathway inhibitors used in GC‐resistant T‐cell acute lymphoblastic leukemia (T‐ALL) . Additionally, reliability of the top enriched pathway associated with GC resistance, Transcriptional misregulation in cancer, is further supported by studies reporting that BCL2A1, PAX5, and CXCL8 play important roles in GC‐resistant ALL . Moreover, Pathways in cancer (map05200 on KEGG website) comprised various oncogenesis signaling pathways including MAPK, JAT/STAT, and PI3K‐AKT signaling pathways, which were confirmed to promote development of GC resistance in leukemia by multiple independent studies .…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis of the crucial candidate genes and pathways associated with glucocorticoid resistance in acute lymphoblastic leukemia

et al. 2020

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Glucocorticoids (GC) are the foundation of the chemotherapy regimen in acute lymphoblastic leukemia (ALL). However, resistance to GC is observed more frequently than resistance to other chemotherapy agents in patients with ALL relapse.Moreover, the mechanism underlying the development of GC resistance in ALL has not yet been fully uncovered. In this study, we used bioinformatic analysis methods to integrate the candidate genes and pathways participating in GC resistance in ALL and subsequently verified the bioinformatics findings with in vitro cell experiments.Ninety-nine significant common differentially expressed genes (DEGs) associated with GC resistance were determined by integrating two gene profile datasets, including GC-sensitive and -resistant samples. Using Kyoto Encyclopedia of Genes and Genomes (KEGG) and REACTOME pathways analysis, the signaling pathways in which DEGs were significantly enriched were clustered. The GC resistance-related biologically functional interactions were visualized as DEG-associated Protein-Protein Interaction (PPI) network complexes, with 98 nodes and 127 edges. MYC, a node which displayed the highest connectivity in all edges, was highlighted as the core gene in the PPI network. Increased C-MYC expression was observed in adriamycin-resistant BALL-1/ADR cells, which we demonstrated was also resistant to dexamethasone. These results outlined a panorama in which the solitary and scattered experimental results were integrated and expanded. The potential promising target of the candidate pathways and genes involved in GC resistance of ALL was concomitantly revealed. K E Y W O R D S acute lymphoblastic leukemia, bioinformatic analysis, glucocorticoid resistance, MYC, signaling pathway | 2919 CHEN Et al.

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“…The genes with differentially methylated CpG’s in their promoters were used to identify relevant transcription factors, and several such identified factors have known prominent roles in inflammation, including PAX5, AP4, CREB, IRF2 and XBP1. PAX5 is a transcription factor that regulates various B cell functions including activation of NF-kB [21]. IRF2 (Interferon regulatory factor 2) regulates IFN-β expression and was found to inhibit LPS induced proinflammatory responses [22].…”

Section: Discussionmentioning

confidence: 99%

DNA methylation analysis of porcine mammary epithelial cells reveals differentially methylated loci associated with immune response against Escherichia coli challenge

Sajjanar¹,

Trakooljul²,

Wimmers³

et al. 2019

BMC Genomics

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Background Epigenetic changes such as cytosine (CpG) DNA methylations regulate gene expression patterns in response to environmental cues including infections. Microbial infections induce DNA methylations that play a potential role in modulating host-immune response. In the present study, we sought to determine DNA methylation changes induced by the mastitis causing Escherichia coli ( E. coli ) in porcine mammary epithelial cells (PMEC) . Two time points (3 h and 24 h) were selected based on specific transcriptomic changes during the early and late immune responses, respectively. Results DNA methylation analysis revealed 561 and 898 significant ( P < 0.01) differentially methylated CpG sites at 3 h and 24 h after E. coli challenge in PMEC respectively. These CpG sites mapped to genes that have functional roles in innate and adaptive immune responses. Significantly, hypomethylated CpG sites were found in the promoter regions of immune response genes such as SDF4, SRXN1, CSF1 and CXCL14 . The quantitative transcript estimation indicated higher expression associated with the DNA CpG methylation observed in these immune response genes. Further, E. coli challenge significantly reduced the expression levels of DNMT3a , a subtype of de novo DNA methylation enzyme, in PMEC indicating the probable reason for the hypomethylation observed in the immune response genes. Conclusions Our study revealed E. coli infection induced DNA methylation loci in the porcine genome. The differentially methylated CpGs were identified in the regulatory regions of genes that play important role in immune response. These results will help to understand epigenetic mechanisms for immune regulation during coliform mastitis in pigs. Electronic supplementary material The online version of this article (10.1186/s12864-019-5976-7) contains supplementary material, which is available to authorized users.

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PAX5 interacts with RIP2 to promote NF-κB activation and drug-resistance of B-lymphoproliferative disorders

Cited by 10 publications

References 47 publications

ETS1 is associated with cisplatin resistance through IKKα/NF-κB pathway in cell line MDA-MB-231

ETS1 is associated with cisplatin resistance through IKKα/NF-κB pathway in cell line MDA-MB-231

Integrated bioinformatics analysis of the crucial candidate genes and pathways associated with glucocorticoid resistance in acute lymphoblastic leukemia

DNA methylation analysis of porcine mammary epithelial cells reveals differentially methylated loci associated with immune response against Escherichia coli challenge

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