scholarly journals T cells are influenced by a long non-coding RNA in the autoimmune associated PTPN2 locus

2018 ◽  
Vol 90 ◽  
pp. 28-38 ◽  
Author(s):  
Miranda Houtman ◽  
Klementy Shchetynsky ◽  
Karine Chemin ◽  
Aase Haj Hensvold ◽  
Daniel Ramsköld ◽  
...  
Keyword(s):  
T Cells ◽  
Non Coding Rna ◽  
Long Non Coding Rna

scholarly journals Overexpression of long non coding RNA OR3A4 is associated with altered p38 signalling, morphological and phenotypic changes, and reduced immunogenicity in Barretts Oesophagus

2021 ◽  
Author(s):  
Thomas Nieto ◽  
Yash Sinha ◽  
Qin Qin Zhuang ◽  
Mathew Coleman ◽  
Joanne D Stockton ◽  
...  
Keyword(s):  
T Cells ◽  
P38 Mapk ◽  
Significant Risk ◽  
Oesophageal Adenocarcinoma ◽  
Cellular Phenotype ◽  
Over Expression ◽  
Non Coding Rna ◽  
P38 Mapk Inhibitor ◽  
Long Non Coding Rna ◽  
Mapk Inhibitor

Background: Barretts Oesophagus (BO) presents a particular pathological dilemma, in that patients who have no dysplasia within their BO experience a small but significant risk of malignant progression each year. Screening programmes have attempted to reduce the mortality from BO associated oesophageal adenocarcinoma but cannot predict which BO patients will progress to invasive malignancy. We have previously identified the long non coding RNA, OR3A4, is differentially hypomethylated in progressive BO. We aimed to understand its role in BO pathogenicity Methods: The stable BO cell line CP-A, as well as the oesophageal adenocarcinoma cells line OE-33 was transfected with a lentiviral OR3A4 over-expression vector, and underwent high resolution microscopy, immunofluorescence, RT-qPCR, RNA sequencing, and targeted drug screening with the p38-MAPK inhibitor domipramod to understand the effects of OR3A4 expression on progression. We then compared progressive vs. non-progressive BO samples using quantitative multi-fluorophore (Vectra) immunohistochemistry. Results: Over-expression of OR3A4 in CP-A lines resulted in a hyperproliferative, dysplastic cellular phenotype, with strong over-expression of MAPK and anti-apoptotic pathways at the RNA and protein level, which was sensitive to the p38-MAPK inhibitor domipramod. Vectra immunohistochemistry demonstrated that progressive BO had reduced visibility associated with a reduction in CD8+ T-cells and CD68+ macrophages and reduced CD4+ T-cells in the stomal compartment. Conclusion: The overexpression of OR3A4, which we have previously shown is associated with progressive BO leads to a proliferative dysplastic cellular phenotype associated with increased, reversible MAPK signalling and loss of immune visibility.

scholarly journals Long Non-Coding RNA Regulation of Allogeneic T-Cells

2019 ◽  
Vol 25 (3) ◽  
pp. S294
Author(s):  
Dan Peltier ◽  
Nicolas Robine ◽  
Guoqing Hou ◽  
Katherine Oravecz-Wilson ◽  
Cynthia Zajac ◽  
...  
Keyword(s):  
T Cells ◽  
Rna Regulation ◽  
Non Coding Rna ◽  
Long Non Coding Rna

scholarly journals Long non-coding RNA MEG3 mediates the miR-149-3p/FOXP3 axis by reducing p53 ubiquitination to exert a suppressive effect on regulatory T cell differentiation and immune escape in esophageal cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qi-Rong Xu ◽  
Jian Tang ◽  
Hong-Ying Liao ◽  
Ben-Tong Yu ◽  
Xiang-Yuan He ◽  
...  
Keyword(s):  
T Cells ◽  
Esophageal Cancer ◽  
Cell Differentiation ◽  
T Cell ◽  
Regulatory T Cell ◽  
Immune Escape ◽  
T Cell Differentiation ◽  
Ki 67 ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Background Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been implicated in the progression of esophageal cancer (EC). However, the specific mechanism of the involvement of MEG3 in EC development in relation to the regulation of immune escape remains uncertain. Thus, the aim of the current study was to investigate the effect of MEG3 on EC via microRNA-149-3p (miR-149-3p). Methods Gain- and loss-of-function experiments were initially performed in EC cells in addition to the establishment of a 4-nitroquinoline 1-oxide-induced EC mouse model aimed at evaluating the respective roles of forkhead box P3 (FOXP3), MEG3, miR-149-3p, mouse double minute 2 homolog (MDM2) and p53 in T cell differentiation and immune escape observed in EC. Results EC tissues were found to exhibit upregulated FOXP3 and MDM2 while MEG3, p53 and miR-149-3p were all downregulated. FOXP3 was confirmed to be a target gene of miR-149-3p with our data suggesting it reduced p53 ubiquitination and degradation by means of inhibiting MDM2. P53 was enriched in the promoter of miR-149-3p to upregulate miR-149-3p. The overexpression of MEG3, p53 or miR-149-3p or silencing FOXP3 was associated with a decline in CD25+FOXP3+CD4+ T cells, IL-10+CD4+ T cells and IL-4+CD4+ T cells in spleen tissues, IL-4, and IL-10 levels as well as C-myc, N-myc and Ki-67 expression in EC mice. Conclusion Collectively, MEG3 decreased FOXP3 expression and resulted in repressed regulatory T cell differentiation and immune escape in EC mice by upregulating miR-149-3p via MDM2-mediated p53.

scholarly journals The Long Non-coding RNA Flatr Anticipates Foxp3 Expression in Regulatory T Cells

2018 ◽  
Vol 9 ◽  
Author(s):  
Aleksandra Brajic ◽  
Dean Franckaert ◽  
Oliver Burton ◽  
Simon Bornschein ◽  
Anna L. Calvanese ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Foxp3 Expression ◽  
Non Coding Rna ◽  
Long Non Coding Rna

scholarly journals TMIC-28. LONG NON-CODING RNA EXPRESSION DIFFERS BETWEEN GLIOBLASTOMA PATIENT IMMUNE CELLS AND HEALTHY VOLUNTEERS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi253-vi253
Author(s):  
Anthony Nwankwo ◽  
Victoria Sanchez ◽  
John Lynes ◽  
Xiang Wang ◽  
Gifty Dominah ◽  
...  
Keyword(s):  
T Cells ◽  
Differential Expression ◽  
Immune Cells ◽  
Fold Change ◽  
Differentially Expressed ◽  
Preliminary Review ◽  
Lncrna Expression ◽  
Glioblastoma Patient ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract To improve glioblastoma treatment, improved characterization of the tumor’s immune microenvironment is critical. Aberrant long non-coding RNA (LncRNA) expression has been implicated in the pathogenesis of many cancers, including glioblastoma. Other studies have discovered long non-coding RNAs which regulate immunity. However, lncRNA expression has not been systematically investigated glioblastoma patient immune cells. We aimed to investigate the differential expression of LncRNA and mRNs in the T lymphocytes and monocytes of glioblastoma patients when compared to healthy controls in an unbiased fashion. CD3 and CD14 cells were sorted from PBMC samples from 3 newly diagnosed glioblastoma patients and 3 normal donors, and RNA was extracted from them. These RNA samples were run on the Arraystar Human LncRNA microarray. We found 309 LncRNAs differentially expressed in glioblastoma patient T cells, and 316 in patient monocytes (fold change >2 or £0.5, P£0.05). A preliminary review of this data has revealed upregulation of lncRNAs that have previously been reported to play a role in tumorigenesis, such as MIF12-AS1, VIM-AS1, and WEE2-AS1. Additionally, lncRNAs such as CCDC26 and Hoxa10 that have been implicated in immune cell differentiation and hyperactivity also show differential expression between the two groups. We also found differential expression of 203 mRNA in T cells and 467 in monocytes (fold change ³2 or £0.5, P£0.05). An analysis based on the Kyoto Encyclopedia of Genes and Genomes identified 42 biological pathways that have enrichment of these differentially expressed mRNAs (P£0.05), including the RIG-I-like receptor pathway and toll-like receptor pathway, both implicated in innate immunity in T-cells. This array data will form the template for future single-cell RNA sequencing of tumor-infiltrating immune cells; peripheral immune cells from glioblastoma patients; and immune cells from non-tumorous brain (epilepsy tissue) and blood samples to investigate these differences in greater detail.

scholarly journals Single-cell Long Non-coding RNA Landscape of T Cells in Human Cancer Immunity

2021 ◽  
Author(s):  
Haitao Luo ◽  
Dechao Bu ◽  
Lijuan Shao ◽  
Yang Li ◽  
Liang Sun ◽  
...  
Keyword(s):  
T Cells ◽  
Single Cell ◽  
Human Cancer ◽  
Cancer Immunity ◽  
Non Coding Rna ◽  
Long Non Coding Rna

scholarly journals An Oxidative Stress-Related Gene Pair (CCNB1/PKD1), Competitive Endogenous RNAs, and Immune-Infiltration Patterns Potentially Regulate Intervertebral Disc Degeneration Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuai Cao ◽  
Hao Liu ◽  
Jiaxin Fan ◽  
Kai Yang ◽  
Baohui Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
Intervertebral Disc ◽  
Intervertebral Disc Degeneration ◽  
Related Gene ◽  
Immune Infiltration ◽  
Non Coding Rna ◽  
Competitive Endogenous Rnas ◽  
Long Non Coding Rna ◽  
Oxidative Stress Related Gene

Oxidative stress (OS) irreversibly affects the pathogenesis of intervertebral disc degeneration (IDD). Certain non-coding RNAs act as competitive endogenous RNAs (ceRNAs) that regulate IDD progression. Analyzing the signatures of oxidative stress-related gene (OSRG) pairs and regulatory ceRNA mechanisms and immune-infiltration patterns associated with IDD may enable researchers to distinguish IDD and reveal the underlying mechanisms. In this study, OSRGs were downloaded and identified using the Gene Expression Omnibus database. Functional-enrichment analysis revealed the involvement of oxidative stress-related pathways and processes, and a ceRNA network was generated. Differentially expressed oxidative stress-related genes (De-OSRGs) were used to construct De-OSRG pairs, which were screened, and candidate De-OSRG pairs were identified. Immune cell-related gene pairs were selected via immune-infiltration analysis. A potential long non-coding RNA–microRNA–mRNA axis was determined, and clinical values were assessed. Eighteen De-OSRGs were identified that were primarily related to intricate signal-transduction pathways, apoptosis-related biological processes, and multiple kinase-related molecular functions. A ceRNA network consisting of 653 long non-coding RNA–microRNA links and 42 mRNA–miRNA links was constructed. Three candidate De-OSRG pairs were screened out from 13 De-OSRG pairs. The abundances of resting memory CD4+ T cells, resting dendritic cells, and CD8+ T cells differed between the control and IDD groups. CD8+ T cell infiltration correlated negatively with cyclin B1 (CCNB1) expression and positively with protein kinase D1 (PKD1) expression. CCNB1–PKD1 was the only pair that was differentially expressed in IDD, was correlated with CD8+ T cells, and displayed better predictive accuracy compared to individual genes. The PKD1–miR-20b-5p–AP000797 and CCNB1–miR-212-3p–AC079834 axes may regulate IDD. Our findings indicate that the OSRG pair CCNB1–PKD1, which regulates oxidative stress during IDD development, is a robust signature for identifying IDD. This OSRG pair and increased infiltration of CD8+ T cells, which play important roles in IDD, were functionally associated. Thus, the OSRG pair CCNB1–PKD1 is promising target for treating IDD.

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