scholarly journals Identification of lncRNA-associated competing endogenous RNA networks for occurrence and prognosis of gastric carcinoma

2020 ◽  
Author(s):  
Lianmin Ye ◽  
Wumin Jin
Keyword(s):  
Enrichment Analysis ◽  
Mapk Signaling ◽  
In Vitro Assay ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Public Health Issue ◽  
Competing Endogenous Rna ◽  
Vitro Assay ◽  
Cerna Network

Abstract Background: Gastric cancer (GC) is one of the common digestive malignancies worldwide and causes a severe public health issue. So far, the underlying mechanisms of GC are largely unclear. Thus, our aim is to identify the long non-coding RNA (lncRNA) associated competing endogenous RNA (ceRNA) specialized for occurrence and progression in GC.Methods: The comprehensive online dataset, TCGA, was downloaded and used for identification of differentially expressed (DE) lncRNA, miRNA and mRNA screen with the value of logFC = 1 and FDR < 0.05, respectively. The interactions between lncRNA and miRNA as well mRNA and miRNA were predicted via multiple online databases, such as miRcode and Targetscan. Then the ceRNA network was constructed accompanied with gene set enrichment analysis and survival analysis. In addition, RT-qPCR and in vitro assay was carried out to validate the effect of the hub lncRNAs.Results: We identified 1485 lncRNAs, 312 miRNAs and 4260 mRNAs were differentially expressed between GC and normal tissues, respectively. Then, we generated a ceRNA network with 909 edges and 253 nodes including 76 lncRNA, 18 miRNA and 159 mRNA. This ceRNA network was involved in MET activates PTK2 signalling, MET promotes cell motility and non-integrin membrane-ECM interactions. Next, by univariate and multivariate analysis, there were 9 hub lncRNAs emerged and were associated subnetwork involved in actin filament binding and MAPK signaling pathway. The in vitro assay indicated lncRNA INHBA-AS1 and CCDC144NL-AS1 may positively related to the GC aggressive features, including proliferation, invasion and migration.Conclusion: In summary, we constructed a ceRNA network involved in the GC development. Moreover, we also identified 9 hub lncRNA-associated network related to prognosis of GC and validated two out of them as promising oncogenes. This may provide potential biomarkers or therapeutic target for GC in future.

scholarly journals TNF-α Triggers RIP1/FADD/Caspase-8-Mediated Apoptosis of Astrocytes and RIP3/MLKL-Mediated Necroptosis of Neurons Induced by Angiostrongylus cantonensis Infection

2021 ◽  
Author(s):  
Hongli Zhou ◽  
Minyu Zhou ◽  
Yue Hu ◽  
Yanin Limpanon ◽  
Yubin Ma ◽  
...  
Keyword(s):  
Cell Death ◽  
Enrichment Analysis ◽  
Angiostrongylus Cantonensis ◽  
Gene Set Enrichment Analysis ◽  
Caspase 8 ◽  
Cns Injury ◽  
Vitro Assay ◽  
Tnf Α

AbstractAngiostrongylus cantonensis (AC) can cause severe eosinophilic meningitis or encephalitis in non-permissive hosts accompanied by apoptosis and necroptosis of brain cells. However, the explicit underlying molecular basis of apoptosis and necroptosis upon AC infection has not yet been elucidated. To determine the specific pathways of apoptosis and necroptosis upon AC infection, gene set enrichment analysis (GSEA) and protein–protein interaction (PPI) analysis for gene expression microarray (accession number: GSE159486) of mouse brain infected by AC revealed that TNF-α likely played a central role in the apoptosis and necroptosis in the context of AC infection, which was further confirmed via an in vivo rescue assay after treating with TNF-α inhibitor. The signalling axes involved in apoptosis and necroptosis were investigated via immunoprecipitation and immunoblotting. Immunofluorescence was used to identify the specific cells that underwent apoptosis or necroptosis. The results showed that TNF-α induced apoptosis of astrocytes through the RIP1/FADD/Caspase-8 axis and induced necroptosis of neurons by the RIP3/MLKL signalling pathway. In addition, in vitro assay revealed that TNF-α secretion by microglia increased upon LSA stimulation and caused necroptosis of neurons. The present study provided the first evidence that TNF-α was secreted by microglia stimulated by AC infection, which caused cell death via parallel pathways of astrocyte apoptosis (mediated by the RIP1/FADD/caspase-8 axis) and neuron necroptosis (driven by the RIP3/MLKL complex). Our research comprehensively elucidated the mechanism of cell death after AC infection and provided new insight into targeting TNF-α signalling as a therapeutic strategy for CNS injury.

The Role of PAX2 in Breast Cancer: A Study Based on Bioinformatics Analysis and in Vitro Validation

2021 ◽  
Author(s):  
Shan Yang ◽  
Wei Gao ◽  
Haoqi Wang ◽  
Xi Zhang ◽  
Yunzhe Mi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Migration And Invasion ◽  
Clinical Samples

Abstract Background: Breast cancer (BC) is the most frequently diagnosed cancer in women and is the second most common cancer among newly diagnosed cancers worldwide. Studies have shown that paired box 2 (PAX2) participates in the tumorigenesis of some cancer cells. However, the functions of PAX2 in the BC context are still unclear.Methods: Transcriptome expression profiles and clinicopathological information of BC were download from the TCGA database. Then the expression level and prognostic value in TCGA database were explored. Gene Set Enrichment Analysis (GSEA) and functional enrichment analysis were performed to investigate the functions and pathways of PAX2. Moreover, RT-qPCR was used to determine the expression of PAX2 in BC tissues, and the predictive value of PAX2 in clinical samples was assessed. CCK-8 assay was used to evaluate cell growth. The migration and invasion capacities of cells were assessed by wound healing assay and Transwell assay.Results: PAX2 was up-regulated in the TCGA-BC datasets. GSEA analysis suggested that PAX2 might be involved in the regulation of MAPK signaling pathways and so on. Moreover, PAX2 was overexpressed in BC tissues, and PAX2 expression was associated with menopause. PAX2 deficiency could inhibit the growth, migration, and invasion of BC cells.Conclusion: This study suggested that PAX2 was up-regulated in BC, which inhibited BC cell growth, migration, and invasion. Thus, PAX2 could be a potential therapeutic target for BC.

scholarly journals LINC01018 and SMIM25 sponged miR-182-5p in endometriosis revealed by the ceRNA network construction

2020 ◽  
Vol 34 ◽  
pp. 205873842097630
Author(s):  
Li Jiang ◽  
Mengmeng Zhang ◽  
Sixue Wang ◽  
Yuzhen Xiao ◽  
Jingni Wu ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Protein Protein Interaction ◽  
Cerna Network ◽  
Non Coding Rna ◽  
Differentially Expressed Mirnas ◽  
Long Non Coding Rna

The current study intended to explore the interaction of the long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) under the background of competitive endogenous RNA (ceRNA) network in endometriosis (EMs). The differentially expressed miRNAs (DEmiRs), differentially expressed lncRNA (DELs), and differentially expressed genes (DEGs) between EMs ectopic (EC) and eutopic (EU) endometrium based on three RNA-sequencing datasets (GSE105765, GSE121406, and GSE105764) were identified, which were used for the construction of ceRNA network. Then, DEGs in the ceRNA network were performed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) analysis. Besides, the DEmiRs in the ceRNA network were validated in GSE124010. And the target DELs and DEGs of verified DEmiRs were validated in GSE86534. The correlation of verified DEmiRs, DEGs, and DELs was explored. Moreover, gene set enrichment analysis (GSEA) was applied to investigate the function of verified DEmiRs, DEGs, and DELs. Overall, 1352 DEGs and 595 DELs from GSE105764, along with 27 overlapped DEmiRs between GSE105765 and GSE121406, were obtained. Subsequently, a ceRNA network, including 11 upregulated and 16 downregulated DEmiRs, 7 upregulated and 13 downregulated DELs, 48 upregulated and 46 downregulated DEGs, was constructed. The GO and KEGG pathway analysis showed that this ceRNA network probably was associated with inflammation-related pathways. Furthermore, hsa-miR-182-5p and its target DELs (LINC01018 and SMIM25) and DEGs (BNC2, CHL1, HMCN1, PRDM16) were successfully verified in the validation analysis. Besides, hsa-miR-182-5p was significantly negatively correlated with these target DELs and DEGs. The GSEA analysis implied that high expression of LINC01018, SMIM25, and CHL1, and low expression of hsa-miR-182-5p would activate inflammation-related pathways in endometriosis EU samples. LINC01018 and SMIM25 might sponge hsa-miR-182-5p to upregulate downstream genes such as CHL1 to promote the development of endometriosis.

scholarly journals Development of a prognostic signature based on six immune related lncRNAs for hepatocellular carcinoma.

2020 ◽  
Author(s):  
Ze-bing Song ◽  
Guo-pei Zhang ◽  
shaoqiang li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Prognostic Signature ◽  
Cox Regression Analysis ◽  
Cerna Network

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumor in the world which prognosis is poor. Therefore, a precise biomarker is needed to guide treatment and improve prognosis. More and more studies have shown that lncRNAs and immune response are closely related to the prognosis of hepatocellular carcinoma. The aim of this study was to establish a prognostic signature based on immune related lncRNAs for HCC.Methods: Univariate cox regression analysis was performed to identify immune related lncRNAs, which had negative correlation with overall survival (OS) of 370 HCC patients from The Cancer Genome Atlas (TCGA). A prognostic signature based on OS related lncRNAs was identified by using multivariate cox regression analysis. Gene set enrichment analysis (GSEA) and a competing endogenous RNA (ceRNA) network were performed to clarify the potential mechanism of lncRNAs included in prognostic signature. Results: A prognostic signature based on OS related lncRNAs (AC145207.5, AL365203.2, AC009779.2, ZFPM2-AS1, PCAT6, LINC00942) showed moderately in prognosis prediction, and related with pathologic stage (Stage I&II VS Stage III&IV), distant metastasis status (M0 VS M1) and tumor stage (T1-2 VS T3-4). CeRNA network constructed 15 aixs among differentially expressed immune related genes, lncRNAs included in prognostic signature and differentially expressed miRNA. GSEA indicated that these lncRNAs were involved in cancer-related pathways. Conclusion: We constructed a prognostic signature based on immune related lncRNAs which can predict prognosis and guide therapies for HCC.

scholarly journals Construction of circRNA-miRNA-mRNA Network for Exploring Underlying Mechanisms of Lubrication Disorder

2021 ◽  
Vol 9 ◽  
Author(s):  
Shengnan Cong ◽  
Jinlong Li ◽  
Jingjing Zhang ◽  
Jingyi Feng ◽  
Aixia Zhang ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Control Group ◽  
Sodium Reabsorption ◽  
Cerna Network ◽  
Reporter Assays

Lubrication disorder is a common health issue that manifests as insufficient sexual arousal at the beginning of sex. It often causes physical and psychological distress. However, there are few studies on lubrication disorder, and the complexity of circular RNA (circRNA) and the related competing endogenous RNA (ceRNA) network in lubrication disorder is still poorly known. Therefore, this study aims to build a regulatory circRNA-micro (mi)RNA-mRNA network and explore potential molecular markers of lubrication disorder. In the study, 12 subjects were recruited, including 6 in the lubrication disorder group and 6 in the normal control group. RNA sequencing was exploited to identify the expression profiles of circRNA, miRNA and mRNA between two groups, and then to construct the circRNA-miRNA-mRNA networks. The enrichment analyses of the differentially expressed (DE)-mRNAs were examined via Gene Set Enrichment Analysis (GSEA). Furthermore, the expression level and interactions among circRNA, miRNA, and mRNA were validated using real-time quantitative polymerase chain reaction (RT-qPCR) and dual-luciferase reporter assays. In the results, 73 circRNAs, 287 miRNAs, and 354 target mRNAs were differentially expressed between two groups when taking | Log2 (fold change)| &gt; 1 and P-value &lt; 0.05 as criteria, and then the results of GSEA revealed that DE-mRNAs were linked with “vascular smooth muscle contraction,” “aldosterone regulated sodium reabsorption,” “calcium signaling pathway,” etc. 19 target relationships among 5 circRNAs, 4 miRNAs, and 7 mRNAs were found and constructed the ceRNA network. Among them, hsa-miR-212-5p and hsa-miR-874-3p were demonstrated to be related to the occurrence of lubrication disorder. Eventually, consistent with sequencing, RT-qPCR showed that hsa_circ_0026782 and ASB2 were upregulated while hsa-miR-874-3p was downregulated, and dual-luciferase reporter assays confirmed the interactions among them. In summary, the findings indicate that the circRNA-miRNA-mRNA regulatory network is presented in lubrication disorder, and ulteriorly provide a deeper understanding of the specific regulatory mechanism of lubrication disorder from the perspective of the circRNA-miRNA-mRNA network.

scholarly journals Building a Competing Endogenous RNA Network to Find Potential Long Non-Coding RNA Biomarkers for Pheochromocytoma

2018 ◽  
Vol 51 (6) ◽  
pp. 2916-2924 ◽  
Author(s):  
Ying-Chun Liang ◽  
Yu-Peng Wu ◽  
Dong-Ning Chen ◽  
Shao-Hao Chen ◽  
Xiao-Dong Li ◽  
...  
Keyword(s):  
Digital Gene Expression ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Competing Endogenous Rna ◽  
Cerna Network ◽  
Competing Endogenous Rna Network ◽  
Patient Prognosis

Background/Aims: Accumulating evidence has shown that long non-coding RNAs (lncRNAs) in competing endogenous RNA (ceRNA) networks play crucial roles in tumor survival and patient prognosis; however, studies investigating ceRNA networks in pheochromocytoma (PCC) are lacking. In this study, we investigated the pathogenesis of PCC and whether lncRNAs acting through ceRNAs networks were associated with prognosis. Methods: A total of 183 PCC samples and 3 control samples from The Cancer Genome Atlas database were analyzed. The Empirical Analysis of Digital Gene Expression Data package in R (edgeR) was used to analyze differentially expressed RNAs. Biological processes and pathways functional enrichment analysis were performed based on the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. LncRNA/mRNA/miRNA ceRNA network was constructed by Cytoscape v3.0 software based on the differentially expressed RNAs Survival package in R was used to perform survival analysis. Results: In total, 554 differentially expressed lncRNAs, 1775 mRNAs and 40 miRNAs were selected for further analysis. Subsequently, 23 lncRNAs, 22 mRNAs, and 6 miRNAs were included in the constructed ceRNA network. Meanwhile, two of the 23 lncRNAs (C9orf147 and BSN-AS2) were identified as independent predictors of overall survival in PCC patients (P< 0.05). Conclusion: This study improves the understanding of lncRNA-related ceRNA networks in PCC and suggests that the lncRNAs C9orf147 and BSN-AS2 could be independent prognostic biomarkers and potential therapeutic targets for PCC.

scholarly journals RNA demethylase ALKBH5 promotes tumorigenesis in multiple myeloma via TRAF1-mediated activation of NF-κB and MAPK signaling pathways

Oncogene ◽  
2021 ◽  
Author(s):  
Jianwei Qu ◽  
Yifan Hou ◽  
Qingxiao Chen ◽  
Jing Chen ◽  
Yi Li ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Signaling Pathways ◽  
Critical Role ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Gene Set Enrichment Analysis ◽  
Dependent Manner ◽  
Growth And Survival ◽  
Mapk Signaling Pathways

AbstractN6-methyladenosine (m6A), an internal modification in mRNA, plays a critical role in regulating gene expression. Dysregulation of m6A modifiers promotes oncogenesis through enzymatic functions that disrupt the balance between the deposition and removal of m6A modification on critical transcripts. However, the roles of mRNA m6A in multiple myeloma (MM) are poorly understood. The present study showed that RNA demethylase ALKBH5 was overexpressed in MM and associated with a poor prognosis in MM patients. Knocking down ALKBH5 induced apoptosis and inhibited the growth of MM cells in vitro. Xenograft models and gene set enrichment analysis with patient transcriptome datasets also supported the oncogenic role of ALKBH5 in MM. Mechanistic studies showed that ALKBH5 exerted tumorigenic effects in myeloma in an m6A-dependent manner, and TNF receptor-associated factor 1 (TRAF1) was a critical target of ALKBH5. Specifically, ALKBH5 regulated TRAF1 expression via decreasing m6A abundance in the 3'-untranslated region (3'-UTR) of TRAF1 transcripts and enhancing TRAF1 mRNA stability. As a result, ALKBH5 promoted MM cell growth and survival through TRAF1-mediated activation of NF-κB and MAPK signaling pathways. Collectively, our data demonstrated that ALKBH5 played a critical role in MM tumorigenesis and suggested that ALKBH5 could be a novel therapeutic target in MM.

In Vitro Assay of Platelet Adhesiveness with Washed and Tanned Human Red Cells

1968 ◽  
Vol 20 (03/04) ◽  
pp. 384-396 ◽  
Author(s):  
G Zbinden ◽  
S Tomlin
Keyword(s):  
Platelet Adhesion ◽  
Sodium Citrate ◽  
Blood Platelets ◽  
In Vitro Assay ◽  
Red Cells ◽  
Platelet Adhesiveness ◽  
Vitro Assay ◽  
In Vitro System ◽  
Human Red Cells

SummaryAn in vitro system is described in which adhesion of blood platelets to washed and tannic acid-treated red cells was assayed quantitatively by microscopic observation. ADP, epinephrine and TAME produced a reversible increase in platelet adhesiveness which was antagonized by AMP. With Evans blue, polyanetholsulfonate, phthalanilide NSC 38280, thrombin and heparin at concentrations above 1-4 u/ml the increase was irreversible. The ADP-induced increase in adhesiveness was inhibited by sodium citrate, EDTA, AMP, ATP and N-ethylmaleimide. EDTA, AMP and the SH-blocker N-ethylmaleimide also reduced spontaneous platelet adhesion to red cells. No significant effects were observed with adenosine, phenprocoumon, 5-HT, phthalanilide NSC 57155, various estrogens, progestogens and fatty acids, acetylsalicylic acid and similarly acting agents, hydroxylamine, glucose and KCN. The method may be useful for the screening of thrombogenic and antithrombotic properties of drugs.

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