scholarly journals Construction of ceRNA Coexpression Network and Screening of Molecular Targets in Colorectal Cancer

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):  
Hui Zhao ◽  
Zhanwei Wang ◽  
Xi Yang ◽  
Jin Liu ◽  
Jing Zhuang ◽  
...  

Abstract 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 functioal enrichment analysis. And a lncRNA-miRNA-mRNA network was constructed wich correlated with CRC. RNAs in this network were subjecte 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 reasearches of therapy the CRC. And the lncRNA RP11-108K3.2 and mRNA ONECUT2 may serve novel prognostic predictor of CRC.


2021 ◽  
Vol 11 ◽  
Author(s):  
Aolin Li ◽  
Ying Gan ◽  
Congcong Cao ◽  
Binglei Ma ◽  
Quan Zhang ◽  
...  

N6-Methyladenosine (m6A) is the most widespread internal RNA modification in several species. In spite of latest advances in researching the biological roles of m6A, its function in the development and progression of bladder cancer remains unclear. In this study, we used MeRIPty -55-seq and RNA-seq methods to obtain a comprehensive transcriptome-wide m6A profiling and gene expression pattern in bladder cancer and paired normal adjacent tissues. Our findings showed that there were 2,331 hypomethylated and 3,819 hypermethylated mRNAs, 32 hypomethylated and 105 hypermethylated lncRNAs, and 15 hypomethylated and 238 hypermethylated circRNAs in bladder cancer tissues compared to adjacent normal tissues. Furthermore, m6A is most often harbored in the coding sequence (CDS), with some near the start and stop codons between two groups. Functional enrichment analysis revealed that differentially methylated mRNAs, lncRNAs, and circRNAs were mostly enriched in transcriptional misregulation in cancer and TNF signaling pathway. We also found that different m6A methylation levels of gene might regulate its expression. In summary, our results for the first time provide an m6A landscape of human bladder cancer, which expand the understanding of m6A modifications and uncover the regulation of mRNAs, lncRNAs, and circRNAs through m6A modification in bladder 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.


Author(s):  
Yanxin Liu ◽  
Zhang Feng ◽  
Huaxia Chen

Background: As a tumor suppressor or oncogenic gene, abnormal expression of RUNX family transcription factor 3 (RUNX3) has been reported in various cancers. Introduction: This study aimed to investigate the role of RUNX3 in melanoma. Methods: The expression level of RUNX3 in melanoma tissues was analyzed by immunohistochemistry and the Oncomine database. Based on microarray datasets GSE3189 and GSE7553, differentially expressed genes (DEGs) in melanoma samples were screened, followed by functional enrichment analysis. Gene Set Enrichment Analysis (GSEA) was performed for RUNX3. DEGs that co-expressed with RUNX3 were analyzed, and the transcription factors (TFs) of RUNX3 and its co-expressed genes were predicted. The protein-protein interactions (PPIs) for RUNX3 were analyzed utilizing the GeneMANIA database. MicroRNAs (miRNAs) that could target RUNX3 expression, were predicted. Results : RUNX3 expression was significantly up-regulated in melanoma tissues. GSEA showed that RUNX3 expression was positively correlated with melanogenesis and melanoma pathways. Eleven DEGs showed significant co-expression with RUNX3 in melanoma, for example, TLE4 was negatively co-expressed with RUNX3. RUNX3 was identified as a TF that regulated the expression of both itself and its co-expressed genes. PPI analysis showed that 20 protein-encoding genes interacted with RUNX3, among which 9 genes were differentially expressed in melanoma, such as CBFB and SMAD3. These genes were significantly enriched in transcriptional regulation by RUNX3, RUNX3 regulates BCL2L11 (BIM) transcription, regulation of I-kappaB kinase/NF-kappaB signaling, and signaling by NOTCH. A total of 31 miRNAs could target RUNX3, such as miR-326, miR-330-5p, and miR-373-3p. Conclusion: RUNX3 expression was up-regulated in melanoma and was implicated in the development of melanoma.


2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Siying He ◽  
Hui Sun ◽  
Yifang Huang ◽  
Shiqi Dong ◽  
Chen Qiao ◽  
...  

Purpose. MiRNAs have been widely analyzed in the occurrence and development of many diseases, including pterygium. This study aimed to identify the key genes and miRNAs in pterygium and to explore the underlying molecular mechanisms. Methods. MiRNA expression was initially extracted and pooled by published literature. Microarray data about differentially expressed genes was downloaded from Gene Expression Omnibus (GEO) database and analyzed with the R programming language. Functional and pathway enrichment analyses were performed using the database for Annotation, Visualization and Integrated Discovery (DAVID). The protein-protein interaction network was constructed with the STRING database. The associations between chemicals, differentially expressed miRNAs, and differentially expressed genes were predicted using the online resource. All the networks were constructed using Cytoscape. Results. We found that 35 miRNAs and 301 genes were significantly differentially expressed. Functional enrichment analysis showed that upregulated genes were significantly enriched in extracellular matrix (ECM) organization, while downregulated genes were mainly involved in cell death and apoptotic process. Finally, we concluded the chemical-gene affected network, miRNA-mRNA interacted networks, and significant pathway network. Conclusion. We identified lists of differentially expressed miRNAs and genes and their possible interaction in pterygium. The networks indicated that ECM breakdown and EMT might be two major pathophysiological mechanisms and showed the potential significance of PI3K-Akt signalling pathway. MiR-29b-3p and collagen family (COL4A1 and COL3A1) might be new treatment target in pterygium.


2021 ◽  
Vol 36 ◽  
pp. 153331752110217
Author(s):  
Liu Lu ◽  
Wen-Zhuo Dai ◽  
Xi-Chen Zhu ◽  
Tao Ma

This paper was aimed to analyze the microRNA (miRNA) signatures in Alzheimer disease (AD) and find the significant expressions of miRNAs, their target genes, the functional enrichment analysis of the confirmed genes, and potential drug treatment. The miRNA expression information of the gene expression profile data was downloaded from the Gene Expression Omnibus database. The total data sample size is 1309, including 1021 AD samples and 288 normal samples. A total of 21 differentially expressed miRNAs were obtained, of which 16 (hsa-miR-6761-3p, hsa-miR-6747-3p, hsa-miR-6875-3p, hsa-miR-6754-3p, hsa-miR-6736-3p, hsa-miR-6762-3p, hsa-miR-6787-3p, hsa-miR-208a-5p, hsa-miR-6740-3p, hsa-miR-6778-3p, hsa-miR-595, hsa-miR-6753-3p, hsa-miR-4747-3p, hsa-miR-3646, hsa-miR-6716-3p and hsa-miR-4435) were up-regulated and 5 (hsa-miR-125a-3p, hsa-miR-22-3p, hsa-miR-24-3p, hsa-miR-6131 and hsa-miR-125b-1-3p) were down-regulated in AD. A total of 6 miRNAs (hsa-miR-595, hsa-miR-3646, hsa-miR-4435 hsa-miR-125a-3p, hsa-miR-22-3p and hsa-miR-24-3p) and 78 miRNA-disease-related gene sub-networks were predicted, and 116 ceRNA regulatory relationship pairs, and the ceRNA regulatory network were obtained. The results of enrichment analysis suggested that the main target pathways of several miRNAs differentially expressed in AD were mitogen-activated protein kinase signal pathway. According to the prediction results of Drug-Gene Interaction database 2.0, we obtained 53 pairs of drug-gene interaction, including 7 genes (PTGS2, EGFR, CALM1, PDE4D, FGFR2, HMGCR, cdk6) and 53 drugs. We hope our results are helpful to find a viable way to prevent, delay the onset, diagnose, and treat AD.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ke-zhi Li ◽  
Yi-xin Yin ◽  
Yan-ping Tang ◽  
Long Long ◽  
Ming-zhi Xie ◽  
...  

Abstract Background Cancers located on the right and left sides of the colon have distinct clinical and molecular characteristics. This study aimed to explore the regulatory mechanisms of location-specific long noncoding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) in colon cancer and identify potential prognostic biomarkers. Method Differentially expressed lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs) between right- and left-side colon cancers were identified by comparing RNA sequencing profiles. Functional enrichment analysis was performed for the DEGs, and a ceRNA network was constructed. Associations between DELs and patient survival were examined, and a DEL-based signature was constructed to examine the prognostic value of these differences. Clinical colon cancer tissues and Gene Expression Omnibus (GEO) datasets were used to validate the results. Results We identified 376 DELs, 35 DEMs, and 805 DEGs between right- and left-side colon cancers. The functional enrichment analysis revealed the functions and pathway involvement of DEGs. A ceRNA network was constructed based on 95 DEL–DEM–DEG interactions. Three DELs (LINC01555, AC015712, and FZD10-AS1) were associated with the overall survival of patients with colon cancer, and a prognostic signature was established based on these three DELs. High risk scores for this signature indicated poor survival, suggesting that the signature has prognostic value for colon cancer. Examination of clinical colon cancer tissues and GEO dataset analysis confirmed the results. Conclusion The ceRNA regulatory network suggests roles for location-specific lncRNAs in colon cancer and allowed the development of an lncRNA-based prognostic signature, which could be used to assess prognosis and determine treatment strategies in patients with colon cancer.


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.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hao Zhang ◽  
Ce Bian ◽  
Simei Tu ◽  
Fanxing Yin ◽  
Panpan Guo ◽  
...  

Abstract Background Many studies on long chain non-coding RNAs (lncRNAs) are published in recent years. But the roles of lncRNAs in aortic dissection (AD) are still unclear and should be further examined. The present work focused on determining the molecular mechanisms underlying lncRNAs regulation in aortic dissection on the basis of the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network. Methods This study collected the lncRNAs (GSE52093), mRNAs (GSE52093) and miRNAs (GSE92427) expression data within human tissue samples with aortic dissection group and normal group based on Gene Expression Omnibus (GEO) database. Results This study identified three differentially expressed lncRNAs (DELs), 19 differentially expressed miRNAs (DEmiRs) and 1046 differentially expressed mRNAs (DEGs) identified regarding aortic dissection. Furthermore, we constructed a lncRNA-miRNA-mRNA network through three lncRNAs (including two with up-regulation and one with down-regulation), five miRNAs (five with up-regulation), as well as 211 mRNAs (including 103 with up-regulation and 108 with down-regulation). Simultaneously, we conducted functional enrichment and pathway analyses on genes within the as-constructed ceRNA network. According to our PPI/ceRNA network and functional enrichment analysis results, four critical genes were found (E2F2, IGF1R, BDNF and PPP2R1B). In addition, E2F2 level was possibly modulated via lncRNA FAM87A-hsa-miR-31-5p/hsa-miR-7-5p or lncRNA C9orf106-hsa-miR-7-5p. The expression of IGF1R may be regulated by lncRNA FAM87A-hsa-miR-16-5p/hsa-miR-7-5p or lncRNA C9orf106-hsa-miR-7-5p. Conclusion In conclusion, the ceRNA interaction axis we identified is a potentially critical target for treating AD. Our results shed more lights on the possible pathogenic mechanism in AD using a lncRNA-associated ceRNA network.


2019 ◽  
Vol 26 (1) ◽  
pp. 107327481983126 ◽  
Author(s):  
Bin Zhao ◽  
Zulqarnain Baloch ◽  
Yunhan Ma ◽  
Zheng Wan ◽  
Yani Huo ◽  
...  

This study was designed to identify the potential key protein interaction networks, genes, and correlated pathways in early-onset colorectal cancer (CRC) via bioinformatics methods. We selected microarray data GSE4107 consisting 12 patient’s colonic mucosa and 10 healthy control mucosa; initially, the GSE4107 were downloaded and analyzed using limma package to identify differentially expressed genes (DEGs). A total of 131 DEGs consisting of 108 upregulated genes and 23 downregulated genes of patients in early-onset CRC were selected by the criteria of adjusted P values <.01 and |log2 fold change (FC)| ≥ 2. The gene ontology functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were accomplished to view the biological process, cellular components, molecular function, and the KEGG pathways of DEGs. Finally, protein–protein interactions (PPIs) were constructed, and the hub protein module was identified. Genes such as ACTA2, ACTG2, MYH11, CALD1, MYL9, TPM2, and LMOD1 were strongly implicated in CRC. In summary, in this study, we indicated that molecular mechanisms were involved in muscle contraction and vascular smooth muscle contraction signaling pathway, which improve our understanding of CRC and could be used as new therapeutic targets for CRC.


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