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 ◽  
...  

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.

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Fuqiang Zu ◽  
Peng Liu ◽  
Huaitao Wang ◽  
Ting Zhu ◽  
Jian Sun ◽  
...  

Abstract Background It is well acknowledged that cancer-related pathways play pivotal roles in the progression of pancreatic cancer (PC). Employing Integrated analysis, we aim to identify the pathway-related ceRNA network associated with PC progression. Methods We divided eight GEO datasets into three groups according to their platform, and combined TCGA and GTEx databases as a group. Additionally, we screened out the differentially expressed genes (DEGs) and performed functional enrichment analysis in each group, and recognized the top hub genes in the most enriched pathway. Furthermore, the upstream of miRNAs and lncRNAs were predicted and validated according to their expression and prognostic roles. Finally, the co-expression analysis was applied to identify a pathway-related ceRNA network in the progression of PC. Results A total of 51 significant pathways that common enriched in all groups were spotted. Enrichment analysis indicated that pathway in cancer was greatly linked with tumor formation and progression. Next, the top 20 hug genes in this pathway were recognized, and stepwise prediction and validation from mRNA to lncRNA, including 11 hub genes, 4 key miRNAs, and 2 key lncRNAs, were applied to identify a meaningful ceRNA network according to ceRNA rules. Ultimately, we identified the PVT1/miR-20b/CCND1 axis as a promising pathway-related ceRNA axis in the progression of PC. Conclusion Overall, we elucidate the pathway-related ceRNA regulatory network of PVT1/miR-20b/CCND1 in the progression of PC, which can be considered as therapeutic targets and encouraging prognostic biomarkers for PC.


2020 ◽  
Author(s):  
Fuqiang Zu ◽  
Peng Liu ◽  
Huaitao Wang ◽  
Ting Zhu ◽  
Jian Sun ◽  
...  

Abstract Background: It is well acknowledged that cancer-related pathways play pivotal roles in the progression of pancreatic cancer (PC). Employing Integrated analysis, we aim to identify the pathway-related ceRNA network associated with PC progression.Methods: We divided eight GEO datasets into three groups according to their platform, and combined TCGA and GTEx databases as a group. Additionally, we screened out the differentially expressed genes (DEGs) and performed functional enrichment analysis in each group, and recognized the top hub genes in the most enriched pathway. Furthermore, the upstream of miRNAs and lncRNAs were predicted and validated according to their expression and prognostic roles. Finally, the co-expression analysis was applied to identify a pathway-related ceRNA network in the progression of PC.Results: A total of 51 significant pathways that common enriched in all groups were spotted. Enrichment analysis indicated that pathway in cancer was greatly linked with tumor formation and progression. Next, the top 20 hug genes in this pathway were recognized, and stepwise prediction and validation from mRNA to lncRNA, including 11 hub genes, 4 key miRNAs, and 2 key lncRNAs, were applied to identify a meaningful ceRNA network according to ceRNA rules. Ultimately, we identified the PVT1/miR-20b-/CCND1 axis as a promising pathway-related ceRNA axis in the progression of PC.Conclusion: Overall, we elucidate the pathway-related ceRNA regulatory network of PVT1/miR-20b-/CCND1 in the progression of PC, which can be considered as therapeutic targets and encouraging prognostic biomarkers for PC.


2020 ◽  
Author(s):  
Fuqiang Zu ◽  
Peng Liu ◽  
Huaitao Wang ◽  
Ting Zhu ◽  
Jian Sun ◽  
...  

Abstract Background: It is well acknowledged that cancer-related pathways play pivotal roles in the progression of pancreatic cancer (PC). Employing Integrated analysis, we aim to identify the pathway-related ceRNA network associated with PC progression.Methods: We divided eight GEO datasets into three groups according to their platform, and combined TCGA and GTEx databases as a group. Additionally, we screened out the differentially expressed genes (DEGs) and performed functional enrichment analysis in each group, and recognized the top hub genes in the most enriched pathway. Furthermore, the upstream of miRNAs and lncRNAs were predicted and validated according to their expression and prognostic roles. Finally, the co-expression analysis was applied to identify a pathway-related ceRNA network in the progression of PC.Results: A total of 51 significant pathways that common enriched in all groups were spotted. Enrichment analysis indicated that pathway in cancer was greatly linked with tumor formation and progression. Next, the top 20 hug genes in this pathway were recognized, and stepwise prediction and validation from mRNA to lncRNA, including 11 hub genes, 4 key miRNAs, and 2 key lncRNAs, were applied to identify a meaningful ceRNA network according to ceRNA rules. Ultimately, we identified the PVT1/miR-20b-/CCND1 axis as a promising pathway-related ceRNA axis in the progression of PC.Conclusion: Overall, we elucidate the pathway-related ceRNA regulatory network of PVT1/miR-20b-/CCND1 in the progression of PC, which can be considered as therapeutic targets and encouraging prognostic biomarkers for PC.


2020 ◽  
Author(s):  
Xiaodong Tan ◽  
Fuqiang Zu ◽  
Peng Liu ◽  
Huaitao Wang ◽  
Ting Zhu ◽  
...  

Abstract Background It is well acknowledged that cancer-related pathways play pivotal roles in the progression of pancreatic cancer (PC). Employing multi-omics analysis, we aim to identify the pathway-related ceRNA network associated with PC progression. Methods We divided eight GEO datasets into three groups according to their platform, and combined TCGA and GTEx databases as a group. Additionally, we screened out the differentially expressed genes (DEGs) and performed functional enrichment analysis in each group, and recognized the top hub genes in the most enriched pathway. Furthermore, the upstream of miRNAs and lncRNAs were predicted and validated according to their expression and prognostic roles. Finally, the co-expression analysis was applied to identify a pathway-related ceRNA network in the progression of PC. Results A total of 51 significant pathways that common enriched in all groups were spotted. Enrichment analysis indicated that pathway in cancer was greatly linked with tumor formation and progression. Next, the top 20 hug genes in this pathway were recognized, and stepwise prediction and validation from mRNA to lncRNA, including 11 hub genes, 4 key miRNAs, and 2 key lncRNAs, were applied to identify a meaningful ceRNA network according to ceRNA rules. Ultimately, we identified the PVT1/miR-20b-/CCND1 axis as a promising pathway-related ceRNA axis in the progression of PC. Conclusion Overall, we elucidate the pathway-related ceRNA regulatory network of PVT1/miR-20b-/CCND1 in the progression of PC, which can be considered as therapeutic targets and encouraging prognostic biomarkers for PC.


2020 ◽  
Author(s):  
Gaochen Lan ◽  
Xiaoling Yu ◽  
Yanna Zhao ◽  
Jinjian Lan ◽  
Wan Li ◽  
...  

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.


2021 ◽  
Vol 8 ◽  
Author(s):  
Yongxin Li ◽  
Yu Meng ◽  
Yuanhang Liu ◽  
Andre J. van Wijnen ◽  
Alfonso Eirin ◽  
...  

Metabolic syndrome (MetS), a collective cluster of disease risk factors that include dyslipidemia, obesity, inflammation, hypertension, and insulin resistance, affects numerous people worldwide. Accumulating studies have shown that long non-coding RNAs (lncRNAs) serve as competing endogenous RNAs (ceRNAs) to play essential roles in regulating gene expression in various diseases. To explore the role of lncRNAs as ceRNAs in MetS, we examined a MetS-associated network in circulating extracellular vesicles (EVs) collected from the systemic blood of MetS and control patients (n = 5 each). In total, 191 differentially expressed lncRNAs, 1,389 mRNAs, and 138 miRNAs were selected for further analysis. Biological processes and pathway functional enrichment analysis were performed based on the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The lncRNA/mRNA/miRNA ceRNA network was constructed by Cytoscape v3.8 based on the DE-RNAs and included 13 lncRNAs, 8 miRNAs, and 64 mRNAs. MetS patients showed elevated body weight, glucose, blood pressure, insulin, liver injury, and inflammatory marker levels. We found that lncRNAs reflect a ceRNA network that may regulate central cellular processes and complications of MetS, including cancer. These findings suggest that MetS alters the interactions among the ceRNA network components in circulating EVs and that this cargo of circulating EVs may have potential translational ramifications for MetS.


2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Lixian Chen ◽  
Zhonglu Ren ◽  
Yongming Cai

Increasing evidence has shown that noncoding RNAs play significant roles in the initiation, progression, and metastasis of tumours via participating in competing endogenous RNA (ceRNA) networks. However, the survival-associated ceRNA in lung adenocarcinoma (LUAD) remains poorly understood. In this study, we aimed to investigate the regulatory mechanisms underlying ceRNA in LUAD to identify novel prognostic factors. mRNA, lncRNA, and miRNA sequencing data obtained from the GDC data portal were utilized to identify differentially expressed (DE) RNAs. Survival-related RNAs were recognized using univariate Kaplan-Meier survival analysis. We performed functional enrichment analysis of survival-related mRNAs using the clusterProfiler package of R and STRING. lncRNA-miRNA and miRNA-mRNA interactions were predicted based on miRcode, Starbase, and miRanda. Subsequently, the survival-associated ceRNA network was constructed for LUAD. Multivariate Cox regression analysis was used to identify prognostic factors. Finally, we acquired 15 DE miRNAs, 49 DE lncRNAs, and 843 DE mRNAs associated with significant overall survival. Functional enrichment analysis indicated that survival-related DE mRNAs were enriched in cell cycle. The survival-associated lncRNA-miRNA-mRNA ceRNA network was constructed using five miRNAs, 49 mRNAs, and 21 lncRNAs. Furthermore, seven hub RNAs (LINC01936, miR-20a-5p, miR-31-5p, TNS1, TGFBR2, SMAD7, and NEDD4L) were identified based on the ceRNA network. LINC01936 and miR-31-5p were found to be significant using the multifactorial Cox regression model. In conclusion, we successfully constructed a survival-related lncRNA-miRNA-mRNA ceRNA regulatory network in LUAD and identified seven hub RNAs, which provide novel insights into the regulatory molecular mechanisms associated with survival of LUAD, and identified two independent prognostic predictors for LUAD.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Zhao Hui ◽  
Wang Zhanwei ◽  
Yang Xi ◽  
Liu Jin ◽  
Zhuang Jing ◽  
...  

Objective. To screen some RNAs that correlated with colorectal cancer (CRC). Methods. Differentially expressed miRNAs, lncRNAs, and mRNAs between cancer tissues and normal tissues in CRC were identified using data from the Gene Expression Omnibus (GEO) database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interactions (PPIs) were performed to do the functional enrichment analysis. And a lncRNA-miRNA-mRNA network was constructed which correlated with CRC. RNAs in this network were subjected to analyze the relationship with the patient prognosis. Results. A total of 688, 241, and 103 differentially expressed genes (diff-mRNA), diff-lncRNA, and diff-miRNA were obtained between cancer tissues and normal tissues. A total of 315 edges were obtained in the ceRNA network. lncRNA RP11-108K3.2 and mRNA ONECUT2 correlated with prognosis. Conclusion. The identified RNAs and constructed ceRNA network could provide great sources for the researches of therapy of the CRC. And the lncRNA RP11-108K3.2 and mRNA ONECUT2 may serve as a novel prognostic predictor of CRC.


2019 ◽  
Author(s):  
fucai tang ◽  
zechao Lu ◽  
jiamin wang ◽  
zhibiao Li ◽  
weijia Wu ◽  
...  

Abstract Background Competitive endogenous RNA (ceRNA) have revealed a new mechanism of interaction between RNAs. However, such comprehension of the ceRNA regulatory network in wilms tumor remains limited. Methods Raw RNA sequencing profiles regarding mRNAs, miRNAs and lncRNAs on wilms tumor samples and normal samples were obtained from Therapeutically Applicable Research to Generate Effective Treatment (TARGET). EdgeR package was applied to identify differentially expressed lncRNAs, miRNAs and mRNAs. Functional enrichment analysis were conducted via DAVID database and the ClusterProfile R package. The lncRNA–miRNA–mRNA interaction ceRNA network was established in Cytoscape according to the identified lncRNAs–miRNAs and miRNAs–mRNAs interactions. Subsequently, correlation between ceRNA network and overall survival prognosis were analyzed. Results A total of 2,037 lncRNAs, 154 miRNAs and 3,609 mRNAs were identified as differentially expressed RNAs in wilms tumor. 205 lncRNAs, 26 miRNAs and 143 mRNAs were included in ceRNA regulatory network. Analysis results showed that 14 out of the 205 lncRNAs, 1 out of 26 miRNAs and 8 out of 143 mRNAs were associated with overall survival in wilms tumor patients (P < 0.05). Conclusions CeRNA networks played an important role in wilms tumor. This might provide effective bioinformatics basis and novel insights for further understanding of the mechanisms underlying wilms tumor.


Author(s):  
Dulari Jayarathna ◽  
Miguel E. Rentería ◽  
Emilie Sauret ◽  
Jyotsna Batra ◽  
Neha S. Gandhi

The discovery of microRNAs (miRNAs) has fundamentally transformed our understanding of gene regulation. The competing endogenous RNA (ceRNA) hypothesis postulates that not only messenger RNAs but also other RNA transcripts, such as long non-coding RNAs and pseudogenes, can act as natural miRNA sponges. These RNAs influence each other&rsquo;s expression levels by competing for the same pool of miRNAs through miRNA response elements on their target transcripts, thereby modulating gene expression and protein activity. In recent years, these ceRNA regulatory networks have gained considerable attention in cancer research. Several studies have identified cancer-specific ceRNA networks. Nevertheless, prior bioinformatic analyses have focused on long non-coding RNAs-associated ceRNA networks. Here, we identify an extended-ceRNA network (including both long non-coding RNAs and pseudogenes) shared across a group of four hormone-dependent (HD) cancers, i.e., prostate, breast, colorectal, and endometrial cancers, using data from The Cancer Genome Atlas (TCGA). We performed a functional enrichment analysis for differentially expressed genes in the shared ceRNA network of HD cancers, followed by a survival analysis to determine their prognostic ability. We identified two long non-coding RNAs, nine genes, and seventy-four miRNAs in the shared ceRNA network across four HD cancers. Among them, two genes and forty-one miRNAs were associated with at least one HD cancer survival. This study is the first to investigate pseudogene associated ceRNAs across a group of related cancers and highlights the value of this approach to understanding shared molecular pathogenesis in a group of related diseases.


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