scholarly journals Exosomes derived from exhausted CD8+ T cells impaired the anticancer function of normal CD8+ T cells

2018 ◽  
Vol 56 (1) ◽  
pp. 29-31 ◽  
Author(s):  
Xiaochen Wang ◽  
Haiyuan Shen ◽  
Qifeng He ◽  
Wenfang Tian ◽  
Anliang Xia ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Expression Profiles ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Interferon Γ ◽  
Functional Enrichment ◽  
Lncrna Expression

BackgroundPrevious studies suggested that diverse cells in cancer microenvironment can interact with CD8+ T cells via exosomes. We designed this study to explore the potential interaction between exhausted CD8+ T cells and normal CD8+ T cells via exosome.MethodsFluorescence activated cell sorting was used to get PD1+TIM3+/PD1−TIM3−CD8+ T cells. Exosomes from the cell culture medium were collected by ultracentrifugation. Microarrays were performed to analyse the lncRNA expression profile in exosomes.ResultsFunctional exhausted CD8+ T cells could secrete vast exosomes, which can be uptake by normal CD8+ T cells, and impaired their proliferation (Ki67), cell activity (CD69) and the production of cytokines such as interferon-γ and interleukin-2. Microarray detection identified 257 candidate lncRNAs differently expressed in exosomes derived from exhausted CD8+ T cells and non-exhausted CD8+ T cells. Functional enrichment analysis indicated that these lncRNAs actively participated in the regulation of diverse process of CD8+ T cell activity, like metabolism, gene expression, biosynthetic process and so forth.ConclusionsThe exosomes derived from exhausted CD8+ T cells could be uptake by non-exhausted CD8+ T cells and subsequently impaired the function of receipt cells. Exosomes secreted from exhausted CD8+ T cells have distinct lncRNA expression profiles which are significantly different from those in exosomes secreted by non-exhausted CD8+ T cells.

scholarly journals Transcriptome profiling of human thymic CD4+ and CD8+ T cells compared to primary peripheral T cells

2019 ◽  
Author(s):  
Hanna Helgeland ◽  
Ingvild Gabrielsen ◽  
Helle Akselsen ◽  
Arvind Y.M. Sundaram ◽  
Siri Tennebø Flåm ◽  
...  
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Valuable Insight ◽  
Thymic Tissue ◽  
Peripheral T Cells

Abstract Background: The thymus is a highly specialized organ of the immune system where T cell precursors develop and differentiate into self-tolerant CD4+ or CD8+ T cells. No studies to date have investigated how the human transcriptome profiles differ, between T cells still residing in the thymus and T cells in the periphery.Results: We have performed high-throughput RNA sequencing to characterize the transcriptomes of primary single positive (SP) CD4+ and CD8+ T cells from infant thymic tissue, as well as primary CD4+ and CD8+ T cells from infant and adult peripheral blood, to enable the comparisons across tissues and ages. In addition, we have assessed the expression of candidate genes related to autoimmune diseases in thymic CD4+ and CD8+ T cells. Thymic SP T cells displayed a broader transcriptome than peripheral T cells, indicated by a higher number of uniquely expressed genes. Comparing T cells of thymic and blood origin, revealed more differentially expressed genes, than between infant and adult blood. Functional enrichment analysis revealed an over-representation of genes involved in cell cycle and replication in thymic T cells, whereas infant blood T cells were dominated by immune related terms. Comparing adult and infant blood T cells, the former was enriched for inflammatory response, cytokine production and biological adhesion, while upregulated genes in infant blood T cells were associated with cell cycle, cell death and gene expression.Conclusion: This study provides valuable insight into the transcriptomes of the human primary SP T cells still residing within the thymus, and offers a unique comparison to the more frequently studied primary blood derived T cells. We discovered that genes involved in migration, homing and recirculation, between peripheral blood and lymphatic tissue, were particularly active in infant blood T cells, suggesting active migration and recirculation in young children.

scholarly journals Identification of Tumorigenic and Prognostic Biomarkers in Colorectal Cancer Based on microRNA Expression Profiles

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuntao Shi ◽  
Yingying Zhuang ◽  
Jialing Zhang ◽  
Mengxue Chen ◽  
Shangnong Wu
Keyword(s):  
Target Genes ◽  
Cox Regression ◽  
Expression Profiles ◽  
Survival Rates ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Risk Groups ◽  
Normal Mucosa ◽  
Microrna Expression ◽  
Functional Enrichment

Objective. Although noncoding RNAs, especially the microRNAs, have been found to play key roles in CRC development in intestinal tissue, the specific mechanism of these microRNAs has not been fully understood. Methods. GEO and TCGA database were used to explore the microRNA expression profiles of normal mucosa, adenoma, and carcinoma. And the differential expression genes were selected. Computationally, we built the SVM model and multivariable Cox regression model to evaluate the performance of tumorigenic microRNAs in discriminating the adenomas from normal tissues and risk prediction. Results. In this study, we identified 20 miRNA biomarkers dysregulated in the colon adenomas. The functional enrichment analysis showed that MAPK activity and MAPK cascade were highly enriched by these tumorigenic microRNAs. We also investigated the target genes of the tumorigenic microRNAs. Eleven genes, including PIGF, TPI1, KLF4, RARS, PCBP2, EIF5A, HK2, RAVER2, HMGN1, MAPK6, and NDUFA2, were identified to be frequently targeted by the tumorigenic microRNAs. The high AUC value and distinct overall survival rates between the two risk groups suggested that these tumorigenic microRNAs had the potential of diagnostic and prognostic value in CRC. Conclusions. The present study revealed possible mechanisms and pathways that may contribute to tumorigenesis of CRC, which could not only be used as CRC early detection biomarkers, but also be useful for tumorigenesis mechanism studies.

scholarly journals miRNA Mediated Noise Making of 3′UTR Mutations in Cancer

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 545 ◽  
Author(s):  
Wei Wu ◽  
Lingxiang Wu ◽  
Mengyan Zhu ◽  
Ziyu Wang ◽  
Min Wu ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
Target Genes ◽  
Expression Profiles ◽  
Tumor Development ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Messenger Rnas ◽  
Cellular Functions ◽  
Mrna Binding

Somatic mutations in 3′-untranslated regions (3′UTR) do not alter amino acids and are considered to be silent in cancers. We found that such mutations can promote tumor progression by altering microRNA (miRNA) targeting efficiency and consequently affecting miRNA–mRNA interactions. We identified 67,159 somatic mutations located in the 3′UTRs of messenger RNAs (mRNAs) which can alter miRNA–mRNA interactions (functional somatic mutations, funcMutations), and 69.3% of these funcMutations (the degree of energy change > 12 kcal/mol) were identified to significantly promote loss of miRNA-mRNA binding. By integrating mRNA expression profiles of 21 cancer types, we found that the expression of target genes was positively correlated with the loss of absolute affinity level and negatively correlated with the gain of absolute affinity level. Functional enrichment analysis revealed that genes carrying funcMutations were significantly enriched in the MAPK and WNT signaling pathways, and analysis of regulatory modules identified eighteen miRNA modules involved with similar cellular functions. Our findings elucidate a complex relationship between miRNA, mRNA, and mutations, and suggest that 3′UTR mutations may play an important role in tumor development.

scholarly journals Identification of a prognostic long non-coding RNA signature in breast cancer

2020 ◽  
Author(s):  
Gaochen Lan ◽  
Xiaoling Yu ◽  
Yanna Zhao ◽  
Jinjian Lan ◽  
Wan Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Cox Regression Analysis

Abstract Background: Breast cancer is the most common malignant disease among women. At present, more and more attention has been paid to long non-coding RNAs (lncRNAs) in the field of breast cancer research. We aimed to investigate the expression profiles of lncRNAs and construct a prognostic lncRNA for predicting the overall survival (OS) of breast cancer.Methods: The expression profiles of lncRNAs and clinical data with breast cancer were obtained from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs were screened out by R package (limma). The survival probability was estimated by the Kaplan‑Meier Test. The Cox Regression Model was performed for univariate and multivariate analysis. The risk score (RS) was established on the basis of the lncRNAs’ expression level (exp) multiplied regression coefficient (β) from the multivariate cox regression analysis with the following formula: RS=exp a1 * β a1 + exp a2 * β a2 +……+ exp an * β an. Functional enrichment analysis was performed by Metascape.Results: A total of 3404 differentially expressed lncRNAs were identified. Among them, CYTOR, MIR4458HG and MAPT-AS1 were significantly associated with the survival of breast cancer. Finally, The RS could predict OS of breast cancer (RS=exp CYTOR * β CYTOR + exp MIR4458HG * β MIR4458HG + exp MAPT-AS1 * β MAPT-AS1). Moreover, it was confirmed that the three-lncRNA signature could be an independent prognostic biomarker for breast cancer (HR=3.040, P=0.000).Conclusions: This study established a three-lncRNA signature, which might be a novel prognostic biomarker for breast cancer.

scholarly journals Identifcation of The Ferroptosis-Related Gene Signature In Placenta of Patients With Early-Onset Preeclampsia

2021 ◽  
Author(s):  
Nana Yang ◽  
Qianghua Wang ◽  
Biao Ding ◽  
Yinging Gong ◽  
Yue Wu ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Late Onset ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Ppi Network ◽  
Network Analyses

Abstract Background: The accumulation of ROS resulting from upregulated levels of oxidative stress is commonly implicated in preeclampsia (PE). Ferroptosis is a novel form of iron-dependent cell death instigated by lipid peroxidation likely plays important role in PE pathogenesis. This study aims to investigate expression profiles and functions of the ferroptosis-related genes (FRGs) in early- and late-onset preeclampsia.Methods: The gene expression data and clinical information were downloaded from GEO database. The “limma” R package was used for screening differentially expressed genes. GO(Gene Ontology), Kyoto Encyclopedia of Genes and Genomes(KEGG) and protein protein interaction (PPI) network analyses were conducted to investigate the bioinformatics functions and molecular interactions of significantly different FRGs. Quantitative real-time reverse transcriptase PCR was used to verify the expression of hub FRGs in PE.Results: A total number of 4,215 DEGs were identified between EOPE and preterm cases and 3,356 DEGs were found between EOPE and LOPE subtypes. 20 significantly different FRGs were identified in EOPE, while only 3 in LOPE. Functional enrichment analysis revealed that the differentially expressed FRGs was mainly involved in EOPE and enriched in hypoxia- and iron-related pathways, such as response to hypoxia, iron homeostasis and iron ion binding process. The PPI network analysis and verification by RT-qPCR resulted in the identification of the following six interesting FRGs: FTH1, HIF1A, FTL, IREB2, MAPK8 and PLIN2. Conclusions: EOPE and LOPE owned distinct underlying molecular mechanisms and ferroptosis may be mainly implicated in pathogenesis of EOPE. Further studies are necessary for deeper inquiry into placental ferroptosis and its role in the pathogenesis of EOPE.

scholarly journals Comparative Transcriptome Analysis Suggests Key Roles for 5-Hydroxytryptamlne Receptors in Control of Goose Egg Production

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 455 ◽  
Author(s):  
Qingyuan Ouyang ◽  
Shenqiang Hu ◽  
Guosong Wang ◽  
Jiwei Hu ◽  
Jiaman Zhang ◽  
...  
Keyword(s):  
Egg Production ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Production Performance ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Anser Anser

To date, research on poultry egg production performance has only been conducted within inter or intra-breed groups, while those combining both inter- and intra-breed groups are lacking. Egg production performance is known to differ markedly between Sichuan white goose (Anser cygnoides) and Landes goose (Anser anser). In order to understand the mechanism of egg production performance in geese, we undertook this study. Here, 18 ovarian stromal samples from both Sichuan white goose and Landes goose at the age of 145 days (3 individuals before egg production initiation for each breed) and 730 days (3 high- and low egg production individuals during non-laying periods for each breed) were collected to reveal the genome-wide expression profiles of ovarian mRNAs and lncRNAs between these two geese breeds at different physiological stages. Briefly, 58, 347, 797, 777, and 881 differentially expressed genes (DEGs) and 56, 24, 154, 105, and 224 differentially expressed long non-coding RNAs (DElncRNAs) were found in LLD vs. HLD (low egg production Landes goose vs. high egg production Landes goose), LSC vs. HSC (low egg production Sichuan White goose vs. high egg production Sichuan white goose), YLD vs. YSC (young Landes goose vs. young Sichuan white goose), HLD vs. HSC (high egg production Landes goose vs. high egg production Sichuan white goose), and LLD vs. LSC (low egg production Landes goose vs. low egg production Sichuan white goose) groups, respectively. Functional enrichment analysis of these DEGs and DElncRNAs suggest that the “neuroactive ligand–receptor interaction pathway” is crucial for egg production, and particularly, members of the 5-hydroxytryptamine receptor (HTR) family affect egg production by regulating ovarian metabolic function. Furthermore, the big differences in the secondary structures among HTR1F and HTR1B, HTR2B, and HTR7 may lead to their different expression patterns in goose ovaries of both inter- and intra-breed groups. These results provide novel insights into the mechanisms regulating poultry egg production performance.

scholarly journals TET2/IDH1/2/WT1 and NPM1 Mutations Influence the RUNX1 Expression Correlations in Acute Myeloid Leukemia

Medicina ◽  
2020 ◽  
Vol 56 (12) ◽  
pp. 637
Author(s):  
Sergiu Pasca ◽  
Ancuta Jurj ◽  
Ciprian Tomuleasa ◽  
Mihnea Zdrenghea
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Mutational Analysis ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Runx1 Expression ◽  
Acute Myeloid

Background and objectives: Mutational analysis has led to a better understanding of acute myeloid leukemia (AML) biology and to an improvement in clinical management. Some of the most important mutations that affect AML biology are represented by mutations in genes related to methylation, more specifically: TET2, IDH1, IDH2 and WT1. Because it has been shown in numerous studies that mutations in these genes lead to similar expression profiles and phenotypes in AML, we decided to assess if mutations in any of those genes interact with other genes important for AML. Materials and Methods: We downloaded the clinical data, mutational profile and expression profile from the TCGA LAML dataset via cBioPortal. Data were analyzed using classical statistical methods and functional enrichment analysis software represented by STRING and GOrilla. Results: The first step we took was to assess the 196 AML cases that had a mutational profile available and observe the mutations that overlapped with TET2/IDH1/2/WT1 mutations. We observed that RUNX1 mutations significantly overlap with TET2/IDH1/2/WT1 mutations. Because of this, we decided to further investigate the role of RUNX1 mutations in modulating the level of RUNX1 mRNA and observed that RUNX1 mutant cases presented higher levels of RUNX1 mRNA. Because there were only 16 cases of RUNX1 mutant samples and that mutations in this gene determined a change in mRNA expression, we further observed the correlation between RUNX1 and other mRNAs in subgroups regarding the presence of hypermethylating mutations and NPM1. Here, we observed that both TET2/IDH1/2/WT1 and NPM1 mutations increase the number of genes negatively correlated with RUNX1 and that these genes were significantly linked to myeloid activation. Conclusions: In the current study, we have shown that NPM1 and TET2/IDH1/2/WT1 mutations increase the number of negative correlations of RUNX1 with other transcripts involved in myeloid differentiation.

scholarly journals Integrated Analyses Identify Immune-Related Signature Associated with Qingyihuaji Formula for Treatment of Pancreatic Ductal Adenocarcinoma Using Network Pharmacology and Weighted Gene Co-Expression Network

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Xiang Qian ◽  
Zhuo Chen ◽  
Sha Sha Chen ◽  
Lu Ming Liu ◽  
Ai Qin Zhang
Keyword(s):  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Ductal Adenocarcinoma ◽  
Network Pharmacology ◽  
Active Ingredients ◽  
Kaplan Meier ◽  
Human Protein Atlas

The study aimed to clarify the potential immune-related targets and mechanisms of Qingyihuaji Formula (QYHJ) against pancreatic cancer (PC) through network pharmacology and weighted gene co-expression network analysis (WGCNA). Active ingredients of herbs in QYHJ were identified by the TCMSP database. Then, the putative targets of active ingredients were predicted with SwissTargetPrediction and the STITCH databases. The expression profiles of GSE32676 were downloaded from the GEO database. WGCNA was used to identify the co-expression modules. Besides, the putative targets, immune-related targets, and the critical module genes were mapped with the specific disease to select the overlapped genes (OGEs). Functional enrichment analysis of putative targets and OGEs was conducted. The overall survival (OS) analysis of OGEs was investigated using the Kaplan-Meier plotter. The relative expression and methylation levels of OGEs were detected in UALCAN, human protein atlas (HPA), Oncomine, DiseaseMeth version 2.0 and, MEXPRESS database, respectively. Gene set enrichment analysis (GSEA) was conducted to elucidate the key pathways of highly-expressed OGEs further. OS analyses found that 12 up-regulated OGEs, including CDK1, PLD1, MET, F2RL1, XDH, NEK2, TOP2A, NQO1, CCND1, PTK6, CTSE, and ERBB2 that could be utilized as potential diagnostic indicators for PC. Further, methylation analyses suggested that the abnormal up-regulation of these OGEs probably resulted from hypomethylation, and GSEA revealed the genes markedly related to cell cycle and proliferation of PC. This study identified CDK1, PLD1, MET, F2RL1, XDH, NEK2, TOP2A, NQO1, CCND1, PTK6, CTSE, and ERBB2 might be used as reliable immune-related biomarkers for prognosis of PC, which may be essential immunotherapies targets of QYHJ.

scholarly journals Protein expression profiles in Meishan and Duroc sows during mid-gestation reveal differences affecting uterine capacity, endometrial receptivity, and the maternal–fetal Interface

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Kejun Wang ◽  
Kaijie Yang ◽  
Qiao Xu ◽  
Yufang Liu ◽  
Wenting Li ◽  
...  
Keyword(s):  
Protein Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Embryonic Mortality ◽  
Functional Enrichment ◽  
Matrix Remodeling ◽  
Swine Industry ◽  
Embryonic Loss

Abstract Background Embryonic mortality is a major concern in the commercial swine industry and primarily occurs early in gestation, but also during mid-gestation (~ days 50–70). Previous reports demonstrated that the embryonic loss rate was significant lower in Meishan than in commercial breeds (including Duroc). Most studies have focused on embryonic mortality in early gestation, but little is known about embryonic loss during mid-gestation. Results In this study, protein expression patterns in endometrial tissue from Meishan and Duroc sows were examined during mid-gestation. A total of 2170 proteins were identified in both breeds. After statistical analysis, 70 and 114 differentially expressed proteins (DEPs) were identified in Meishan and Duroc sows, respectively. Between Meishan and Duroc sows, 114 DEPs were detected at day 49, and 98 DEPs were detected at day 72. Functional enrichment analysis revealed differences in protein expression patterns in the two breeds. Around half of DEPs were more highly expressed in Duroc at day 49 (DUD49), relative to DUD72 and Meishan at day 49 (MSD49). Many DEPs appear to be involved in metabolic process such as arginine metabolism. Our results suggest that the differences in expression affect uterine capacity, endometrial matrix remodeling, and maternal-embryo cross-talk, and may be major factors influencing the differences in embryonic loss between Meishan and Duroc sows during mid-gestation. Conclusions Our data showed differential protein expression pattern in endometrium between Meishan and Duroc sows and provides insight into the development process of endometrium. These findings could help us further uncover the molecular mechanism involved in prolificacy.

scholarly journals miRNASNP-v3: a comprehensive database for SNPs and disease-related variations in miRNAs and miRNA targets

2020 ◽  
Vol 49 (D1) ◽  
pp. D1276-D1281
Author(s):  
Chun-Jie Liu ◽  
Xin Fu ◽  
Mengxuan Xia ◽  
Qiong Zhang ◽  
Zhifeng Gu ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Mirna Target ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Nucleotide Polymorphisms ◽  
Functional Variation ◽  
Single Nucleotide ◽  
Target Binding

Abstract MicroRNAs (miRNAs) related single-nucleotide variations (SNVs), including single-nucleotide polymorphisms (SNPs) and disease-related variations (DRVs) in miRNAs and miRNA-target binding sites, can affect miRNA functions and/or biogenesis, thus to impact on phenotypes. miRNASNP is a widely used database for miRNA-related SNPs and their effects. Here, we updated it to miRNASNP-v3 (http://bioinfo.life.hust.edu.cn/miRNASNP/) with tremendous number of SNVs and new features, especially the DRVs data. We analyzed the effects of 7 161 741 SNPs and 505 417 DRVs on 1897 pre-miRNAs (2630 mature miRNAs) and 3′UTRs of 18 152 genes. miRNASNP-v3 provides a one-stop resource for miRNA-related SNVs research with the following functions: (i) explore associations between miRNA-related SNPs/DRVs and diseases; (ii) browse the effects of SNPs/DRVs on miRNA-target binding; (iii) functional enrichment analysis of miRNA target gain/loss caused by SNPs/DRVs; (iv) investigate correlations between drug sensitivity and miRNA expression; (v) inquire expression profiles of miRNAs and their targets in cancers; (vi) browse the effects of SNPs/DRVs on pre-miRNA secondary structure changes; and (vii) predict the effects of user-defined variations on miRNA-target binding or pre-miRNA secondary structure. miRNASNP-v3 is a valuable and long-term supported resource in functional variation screening and miRNA function studies.

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