scholarly journals Transcriptomic Analysis Revealed an Emerging Role of Alternative Splicing in Embryonal Tumor with Multilayered Rosettes

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1108
Author(s):  
Dina Hesham ◽  
Shahenda El-Naggar
Keyword(s):  
Cell Cycle ◽  
Alternative Splicing ◽  
Wnt Signaling Pathway ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Embryonal Tumor ◽  
Alternative Splicing Events ◽  
Regulation Of Cell Cycle

Embryonal tumor with multilayered rosettes (ETMR) is an aggressive and rare pediatric embryonal brain tumor. Amplification of C19MC microRNA cluster and expression of LIN28 are distinctive features of ETMR. Despite the increasing efforts to decipher ETMR, the biology remains poorly understood. To date, the role of aberrant alternative splicing in ETMR has not been thoroughly investigated. In the current study, a comprehensive analysis was performed on published unprocessed RNA-seq reads of tissue-matched ETMR and fetal controls datasets. Gene expression was quantified in samples using Kallisto/sleuth pipeline. For the alternative splicing analysis, STAR, SplAdder and rMATS were used. Functional enrichment analysis was subsequently performed using Metascape. The expression analysis identified a total of 3622 differentially expressed genes (DEGs) between ETMR and fetal controls while 1627 genes showed differential alternative splicing patterns. Interestingly, genes with significant alternative splicing events in ETMR were identified to be involved in signaling pathways such as ErbB, mTOR and MAPK pathways as well as ubiquitin-mediated proteolysis, cell cycle and autophagy. Moreover, up-regulated DEGs with alternative splicing events were involved in important biological processes including nuclear transport, regulation of cell cycle and regulation of Wnt signaling pathway. These findings highlight the role of aberrant alternative splicing in shaping the ETMR tumor landscape, and the identified pathways constitute potential therapeutic targets.

scholarly journals Prognostic Alternative mRNA Splicing in Adrenocortical Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Weiwei Liang ◽  
Fangfang Sun
Keyword(s):  
Alternative Splicing ◽  
Prediction Model ◽  
Adrenocortical Carcinoma ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Lasso Regression ◽  
Cox Regression Analysis ◽  
Alternative Mrna Splicing ◽  
Alternative Splicing Events

BackgroundThis paper aims to identify alternative RNA splicing landscape and its prognostic value in adrenocortical carcinoma.MethodsThe alternative splicing events data with corresponding clinical information data of 79 ACC patients were obtained from the Cancer Genome Atlas and SpliceSeq package. Prognosis-associated AS events by using univariate Cox regression analysis were selected. Gene functional enrichment analysis demonstrated the potential pathways enriched by survival-associated AS. Prognosis-related splicing events were submitted to develop moderate predictors using Lasso regression model.ResultsOne thousand five survival-associated alternative splicing events were identified. The prognostic genes included ATXN2L, MEIS1, IKBKB, COX4I1. Functional enrichment analysis suggested that prognostic splicing events are associated with Wnt signaling pathway. A prediction model including 12 alternative splicing events was constructed by Lasso regression using train set. ROC analysis showed good performance of the prediction model in test set. Then, a nomogram integrating the clinical-pathological factors and riskscore was constructed for predicting 1‐ and 3‐year survival rate.ConclusionOur data provide a comprehensive bioinformatics analysis of AS events in ACC, providing biomarkers for disease progression and a potentially rich source of novel therapeutic targets.

scholarly journals Role of survival-associated alternative splicing events in the prognosis of ovarian cancer

2021 ◽  
Author(s):  
Congbo Yue ◽  
Tianyi Zhao ◽  
Shoucai Zhang ◽  
Yingjie Liu ◽  
GUIXI ZHENG ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Alternative Splicing ◽  
Cox Regression ◽  
Risk Group ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
High Risk Group ◽  
Functional Enrichment ◽  
Prognostic Models

Abstract Objective Alternative splicing (AS) events play a crucial role in the tumorigenesis and progression of various cancers. In the present study, we aimed to identify specific AS events, which might be prognostic markers and therapeutic targets for ovarian cancer (OV). Methods Transcriptome data, clinical information, and Percent Spliced In (PSI) values were downloaded from TCGA database and TCGA SpliceSeq to explore the role of AS events in the prognosis of OV patients. Univariate and multivariate Cox regression analyses were performed to identify survival-associated AS events and develop multi-AS-based prognostic models. The K-M curves and ROC curves were conducted based on prognostic AS event models. Moreover, a splicing regulatory network was established according to the correlation between AS events and splicing factors (SFs). Finally, we performed functional enrichment analysis by GO terms and KEGG pathways. Results We identified 1,472 AS events that were associated with the survival of OV patients, and exon skipping (ES) was the most important type. We also found that prognostic models based on AS events were good predictors of OV prognosis, which could discriminate the high-risk group from the low-risk group (P < 0.05). Notably, the AUC value of AD, AP, AT, ES, ME, and the whole cohort was more than 0.70, indicating that these six models had valuable prediction strength. The risk score of prognostic models was identified as an independent prognostic factor. Furthermore, the AS-SF correlation network revealed several hub SF genes, including DDX39B, PNN, LUC7L3, ZC3H4 and SRSF11, and so on. Conclusions In the present study, we constructed powerful prognostic predictors for OV patients and uncovered interesting splicing networks. Collectively, our findings provided valuable insights into the underlying mechanisms of OV.

scholarly journals A comprehensive transcriptomic view on the role of SMAD4 gene by RNAi-mediated knockdown in porcine follicular granulosa cells

Reproduction ◽  
2016 ◽  
Vol 152 (1) ◽  
pp. 81-89 ◽  
Author(s):  
Lifan Zhang ◽  
Xing Du ◽  
Shengjuan Wei ◽  
Dongfeng Li ◽  
Qifa Li
Keyword(s):  
Cell Cycle ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Current Knowledge ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment

As a key mediator of the transforming growth factor-beta (TGF-β) signaling pathway, which plays a pivotal role in regulating mammalian reproductive performance, Sma- and Mad-related protein 4 (SMAD4) is closely associated with the development of ovarian follicular. However, current knowledge of the genome-wide view on the role ofSMAD4gene in mammalian follicular granulosa cells (GCs) is still largely unknown. In the present study, RNA-Seq was performed to investigate the effects ofSMAD4knockdown by RNA interference (SMAD4-siRNA) in porcine follicular GCs. A total of 1025 differentially expressed genes (DEGs), including 530 upregulated genes and 495 downregulated genes, were identified inSMAD4-siRNA treated GCs compared with that treated with NC-siRNA. Furthermore, functional enrichment analysis indicated that upregulated DEGs inSMAD4-siRNA treated cells were mainly enriched in cell-cycle related processes, interferon signaling pathway, and immune system process, while downregulated DEGs inSMAD4-siRNA treated cells were mainly involved in extracellular matrix organization/disassembly, pathogenesis, and cell adhesion. In particular, cell cycle and TGF-β signaling pathway were discovered as the canonical pathways changed underSMAD4-silencing. Taken together, our data revealsSMAD4knockdown alters the expression of numerous genes involved in key biological processes of the development of follicular GCs and provides a novel global clue of the role ofSMAD4gene in porcine follicular GCs, thus improving our understanding of regulatory mechanisms ofSMAD4gene in follicular development.

scholarly journals The Role of Circular RNA CDR1as/ciRS-7 in Regulating Tumor Microenvironment: A Pan-Cancer Analysis

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 429 ◽  
Author(s):  
Zou ◽  
Zheng ◽  
Deng ◽  
Yang ◽  
Xie ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Signaling Pathway ◽  
Malignant Tumors ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Circular Rna ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Receptor Interaction

Circular RNA CDR1as/ciRS-7 functions as an oncogenic regulator in various cancers. However, there has been a lack of systematic and comprehensive analysis to further elucidate its underlying role in cancer. In the current study, we firstly performed a bioinformatics analysis of CDR1as among 868 cancer samples by using RNA-seq datasets of the MiOncoCirc database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), CIBERSORT, Estimating the Proportion of Immune and Cancer cells (EPIC), and the MAlignant Tumors using Expression data (ESTIMATE) algorithm were applied to investigate the underlying functions and pathways. Functional enrichment analysis suggested that CDR1as has roles associated with angiogenesis, extracellular matrix (ECM) organization, integrin binding, and collagen binding. Moreover, pathway analysis indicated that it may regulate the TGF-β signaling pathway and ECM-receptor interaction. Therefore, we used CIBERSORT, EPIC, and the ESTIMATE algorithm to investigate the association between CDR1as expression and the tumor microenvironment. Our data strongly suggest that CDR1as may play a specific role in immune and stromal cell infiltration in tumor tissue, especially those of CD8+ T cells, activated NK cells, M2 macrophages, cancer-associated fibroblasts (CAFs) and endothelial cells. Generally, systematic and comprehensive analyses of CDR1as were conducted to shed light on its underlying pro-cancerous mechanism. CDR1as regulates the TGF-β signaling pathway and ECM-receptor interaction to serve as a mediator in alteration of the tumor microenvironment.

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.

Functional Enrichment Analysis by David in Transgenic MYCN Zebrafish Model

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5114-5114
Author(s):  
Li-Jing Shen ◽  
Fang-Yuan Chen ◽  
Lan-Fang Cao ◽  
Yong Zhang ◽  
Hua Zhong
Keyword(s):  
Cell Cycle ◽  
Signaling Pathways ◽  
Microarray Analysis ◽  
Conflicts Of Interest ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Mapk Signaling ◽  
Functional Enrichment ◽  
Tgfβ Signaling ◽  
Apoptosis Pathway

Abstract Abstract 5114 Introduction The MYCN oncogene encodes a basic helix-loop-helix/leucine zipper (bHLH/LZ) transcription factor that is frequently overexpressed in hematologic malignancies neoplasms (including acute leukemia, T-cell lymphoma, and so on). MYCN acts as a poor prognostic marker to promote an aggressive phenotype. However, the mechanisms of action and pathways affected by MYCN are still largely unclear. Methods We induced murine MYCN gene overexpression in embryonic zebrafish through heat-shock promoter and established stable germline Tg(MYCN:HSE:EGFP) zebrafish. RNA was extracted at 3 days post fertilization from wild type (WT) and transgenic zebrafish F1 generation (TG) embryo hematopoietic cells, collected by the flow cytometer, for microarray analysis. The samples were processed and subsequently analyzed in triplicate on Zebrafish Oligo Microarrays (Agilent Technologies), containing 43, 554 sets of probe, at the Advanced Throughput Inc. The microarrays were scanned in an Agilent DNA Microarray Scanner and the images were processed using Feature Extraction software. A False Discovery Rate≤0. 05 for overall interactions effect and P<0. 001 between comparisons were used to determine differentially expressed genes (DEG). Ingenuity Pathway Analysis and DAVID performed the functional analysis of DEG. Results Microarray analysis revealed 626 (342 genes up-regulated and 284 genes down-regulated) DEG that showed >2-fold change in TG comparing with that of WT. Using functional enrichment analysis by DAVID, several signaling pathways were regulated in TG samples (Table 1). MAPK signaling pathway was high activated through FGF, PDGF, BDNF and CACN high expression, promoting up-regulated of Ras and MKP, enhancing phosphorylation and leading to increase of cells proliferation. TGFβ signaling was inhibited by up-regulation of IFN Ã and Smad 6/7, which negative control of TGFβR and Smad 2/3. Further, we found that MYCN enhances the expression of skp2, via decreased p21 and increased CDK2, promoting cell cycle progression (Fig. 1). In addition, overexpression of MYCN weakened the function of mismatch repair, base excision repair, while increased apoptosis pathway mediated by p53 (up-regulated Bid gene). Meanwhile, Glycolysis/gluconeogenesis pathway was significantly up-regulated in TG fish. Conclusions Overexpression of MYCN induced up-regulation of cell proliferation and Glycolysis/gluconeogenesis pathway (as the Warburg effect in rapidly proliferating tumors), attenuation of repair function, all of which are phenomena associated with proliferation and malignancies transformation of blood cell feature. We found that MYCN down-regulates p27kip1, p57kip2 and p21cip1 through up-regulate Skp2, thus up-regulates CDK2, CycA, CycB, CycD and CycE. All above changes shortened the time taken to progress through the cell cycle. Increased MARK signaling and decreased TGFβ signaling pathways also contributed to promote cell cycle. (Red star marks the up-regulated genes). Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Expression and Prognostic Role of Peroxiredoxins in Lung Cancer

2019 ◽  
Author(s):  
Ben Li ◽  
Bo Zhang ◽  
Qiong Wu ◽  
Xinming Chen ◽  
Xiang Cao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Squamous Cell Carcinoma ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Expression Level ◽  
Normal Lung ◽  
Lung Cells ◽  
Analysis Tool

Background: Peroxiredoxins (Prxs) comprise antioxidant factors that are widely found in prokaryotes and eukaryotes. Abnormal expression of Prxs is closely related to tumorigenesis. Methods: This study examined the prognostic value and expression of Prxs in lung cancer by Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan-Meier Plotter, cBioPortal and Functional Enrichment Analysis Tool (FunRich) databases. Results: We found that Prx1/2/3/4/5 were overexpressed in both lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) relative to normal lung cells. However, the expression level of Prx6 was lower in LUAD and higher in LUSC than normal lung cells. The level of Prx3 and Prx6 were associated with pathological stage. Prognostic analysis showed that elevated Prx1 and Prx2 expression were correlated with low Overall Survival (OS), whereas high Prx5 and Prx6 expression level predicted high OS. Conclusions: Our results effectively revealed the level of Prxs in lung cancer and its influence on the prognosis of lung carcinoma, contributing to the study of the role of Prxs in tumorigenesis.

scholarly journals Detecting Hub Genes Associated With Lauren Subtype of Gastric Cancer by Weighted Gene Co-Expression Network Analysis

2020 ◽  
Author(s):  
XU LIU ◽  
Li Yao ◽  
Jingkun Qu ◽  
Lin Liu ◽  
XU LIU ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Network Analysis ◽  
Cancer Survival ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Diffuse Gastric Cancer ◽  
Hub Genes ◽  
Gene Modules

Abstract Background Gastric cancer is a rather heterogeneous type of malignant tumor. Among the several classification system, Lauren classification can reflect biological and pathological differences of different gastric cancer.Method to provide systematic biological perspectives, we employ weighted gene co-expression network analysis to reveal transcriptomic characteristics of gastric cancer. GSE15459 and TCGA STAD dataset were downloaded. Co-expressional network was constructed and gene modules were identified. Result Two key modules blue and red were suggested to be associated with diffuse gastric cancer. Functional enrichment analysis of genes from the two modules was performed. Validating in TCGA STAD dataset, we propose 10 genes TNS1, PGM5, CPXM2, LIMS2, AOC3, CRYAB, ANGPTL1, BOC and TOP2A to be hub-genes for diffuse gastric cancer. Finally these ten genes were associated with gastric cancer survival. Conclusion More attention need to be paid and further experimental study is required to elucidate the role of these genes.

scholarly journals A novel ferroptosis-related gene signature associated with cell cycle for prognosis prediction in patients with clear cell renal cell carcinoma

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Siteng Chen ◽  
Encheng Zhang ◽  
Tuanjie Guo ◽  
Jialiang Shao ◽  
Tao Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Renal Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Related Gene ◽  
Cell Renal Cell Carcinoma ◽  
Prognosis Model

Abstract Background It is of great urgency to explore useful prognostic markers for patients with clear cell renal cell carcinoma (ccRCC). Prognostic models based on ferroptosis-related gene (FRG) in ccRCC is poorly reported for now. Methods Comprehensive analysis of 22 FRGs were performed in 629 ccRCC samples from two independent patient cohorts. We carried out least absolute shrinkage and selection operator analysis to screen out prognosis-related FRGs and constructed prognosis model for patients with ccRCC. Weighted gene co-expression network analysis was also carried out for potential functional enrichment analysis. Results Based on the TCGA cohort, a total of 11 prognosis-associated FRGs were selected for the construction of the prognosis model. Significantly differential overall survival (hazard ratio = 3.61, 95% CI: 2.68–4.87, p < 0.0001) was observed between patients with high and low FRG score in the TCGA cohort, which was further verified in the CPTAC cohort with hazard ratio value of 5.13 (95% CI: 1.65–15.90, p = 0.019). Subgroup survival analysis revealed that our FRG score could significantly distinguish patients with high survival risk among different tumor stages and different tumor grades. Functional enrichment analysis illustrated that the process of cell cycle, including cell cycle-mitotic pathway, cytokinesis pathway and nuclear division pathway, might be involved in the regulation of ccRCC through ferroptosis. Conclusions We developed and verified a FRG signature for the prognosis prediction of patients with ccRCC, which could act as a risk factor and help to update the tumor staging system when integrated with clinicopathological characteristics. Cell cycle-related pathways might be involved in the regulation of ccRCC through ferroptosis.

scholarly journals Comprehensive Analysis of Ferroptosis Regulators in Lung Adenocarcinomas Identifies Prognostic and Immunotherapy-Related Biomarkers

2021 ◽  
Vol 8 ◽  
Author(s):  
Sijin Sun ◽  
Wei Guo ◽  
Fang Lv ◽  
Guochao Zhang ◽  
Juhong Wang ◽  
...  
Keyword(s):  
Risk Score ◽  
Potential Role ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Mutation Burden ◽  
Related Risk ◽  
Lung Adenocarcinomas

Ferroptosis is a newly discovered type of programmed cell death that differs from canonical apoptosis. However, the potential role of ferroptosis in lung adenocarcinoma (LUAD) has not been elaborated. In total, 1,328 samples from databases and 36 ferroptosis regulators were included in this study. By combining random survival forest and principal component analysis algorithms, a robust prognostic ferroptosis-related risk score (FRRS) was constructed, and the performance was validated in three independent datasets. Based on the median risk score, two subgroups were identified. Then, comparisons, including of mutational profiles, functional enrichment analyses and immune components, were conducted between subgroups. An immunotherapy cohort was applied to explore potential therapeutic-related biomarkers. Finally, the clinical utility of FRRS was validated in a proteomic cohort. In the TCGA-LUAD cohort, FRRS was calculated using the expression of 11 selected genes, and patients with high FRRS had a significantly (p &lt; 0.001) worse prognosis than those with low FRRS. Multivariate regression suggested that FRRS was an independent prognostic factor. Functional enrichment analysis indicated that FRRS was mainly involved in cell cycle, metabolic and immune-related pathways. Furthermore, FRRS was shown to be significantly (p &lt; 0.001) associated with the abundance of CD8 T cells and tumor mutation burden (TMB). The combination of TMB and FANCD2 expression, the main contributor to FRRS, substantially increased the precision of predicting the therapeutic response. In conclusion, the present study revealed the potential role of ferroptosis regulators in LUAD and identified ferroptosis-related biomarkers for prognostic and immunotherapeutic predictions.

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