scholarly journals Comprehensive Analysis of Competing Endogenous RNA (ceRNA) Network Based on RNAs Differentially Expressed in Lung Adenocarcinoma Using The Cancer Genome Atlas (TCGA) Database

2020 ◽  
Vol 26 ◽  
Author(s):  
Huaihui Tang ◽  
Zhongshuai Wang ◽  
Qianqian Shao ◽  
Yue Wang ◽  
Qingshan Yang
2022 ◽  
Vol 12 ◽  
Author(s):  
Wen Wang ◽  
Hao Bo ◽  
Yumei Liang ◽  
Guoli Li

Lung adenocarcinoma (LUAD) is the most common histological lung cancer, and it is the leading cause of cancer-related deaths worldwide. Long noncoding RNAs (lncRNAs) have been implicated in tumorigenesis. LINC00467 is a novel lncRNA that is abnormally expressed in several cancer types including LUAD. However, its function and regulatory mechanism in LUAD progression remain unclear. In this study, based on The Cancer Genome Atlas data mining, we demonstrated that DNA copy number amplification and hypomethylation was positively correlated with LINC00467 expression in LUAD. In addition, DNA copy number amplification was significantly associated with distant metastasis, immune infiltration and poor survival. Microarray analysis demonstrated that LINC00467 knockdown in the LUAD A549 cell line led to a distinct microRNA expression profile that impacted various target genes involved in multiple biological processes. This finding suggests that LINC00467 may regulate LUAD progression by functioning as a competing endogenous RNA (ceRNA). Finally, we constructed a ceRNA network that included two microRNAs (hsa-miR-1225-5p, hsa-miR-575) and five mRNAs (BARX2, BCL9, KCNK1, KIAA1324, TMEM182) specific to LINC00467 in LUAD. Subsequent Kaplan-Meier survival analysis in both The Cancer Genome Atlas and Gene Expression Omnibus databases revealed that two genes, BARX2 and BCL9, were potential prognostic biomarkers for LUAD patients. In conclusion, our data provide possible mechanisms underlying the abnormal upregulation of LINC00467 as well as a comprehensive view of the LINC00467-mediated ceRNA network in LUAD, thereby highlighting its potential role in diagnosis and therapy.


2020 ◽  
Author(s):  
Guoheng Mo ◽  
Qunguang Jiang ◽  
Zixuan Wang ◽  
Zhaoting Zheng ◽  
XiaoSi Chen

Abstract Increasing evidence indicates that the competitive endogenous RNA (ceRNA) hypothesis, that is, long non-coding RNA (LncRNA) can competitively bind microRNA (miRNA) through miRNA response elements to affect the expression of target RNA, and dysregulation of LncRNA expression plays a key role in tumor progression. The papillary thyroid carcinoma that we studied is the most significant pathological type of thyroid cancer, but its ceRNA network has not been extensively evaluated. We analyzed level-3 data from RNA-Seq of 58 para-carcinoma tissues and 501 patients with primary papillary thyroid carcinoma (PTC) using the DEseq software package and downloaded clinical information from The Cancer Genome Atlas (TCGA) to find potential biomarkers or therapeutic targets. As a result, 149 differential miRNAs were selected, including 117 up -regulated, 32 down-regulated, and 3099 differential mRNAs, including 1976 up-regulated, 1123 down-regulated, and 434 differential lncRNAs, including 331 up-regulated and 103 down-regulated (Fold Change > 2, P < 0.05). The interactions between these differentially expressed RNA groups constitute the ceRNA network of PTC. Moreover, we used the microde database to predict the miRNAs that may be acted by the above screened differential lncRNAs and intersected with the selected miRNAs, and further predicted the target genes of the intersecting miRNAs by TargetScan, miRTarBase and miRDB, and intersected with the selected mRNAs. From the constructed ceRNA network we can see that Linc00460 may cause the invasion and metastasis of PTC by competitively inhibiting hsa-mir-150 and upregulating the expression of its downstream target gene EREG. Our study identified a series of lncRNAs associated with PTC progression and prognosis, and this complex ceRNA interaction network provides guidance for better understanding of the molecular mechanisms of PTC and can be used as an effective diagnostic tool for PTC invasion, metastasis and prognosis. Kaplan-Meier analysis of the differentially expressed RNAs associated with PTC pathogenesis confirmed that the lncRNAs AC097717.1, C20orf203, EMX2OS were potentially associated with the prognosis of PTC (P<0.05).


Epigenomics ◽  
2019 ◽  
Vol 11 (13) ◽  
pp. 1501-1518 ◽  
Author(s):  
Guansheng Zhong ◽  
Weiyang Lou ◽  
Minya Yao ◽  
Chengyong Du ◽  
Haiyan Wei ◽  
...  

Aim: To identify novel competing endogenous RNA (ceRNA) network related to patients prognosis in breast cancer. Materials & methods: Dysregulated mRNA based on intersection of three Gene Expression Omnibus and The Cancer Genome Atlas datasets were analyzed by bioinformatics. Results: In total 72 upregulated and 208 downregulated genes were identified. Functional analysis showed that some pathways related to cancer were significantly enriched. By means of stepwise reverse prediction and validation from mRNA to lncRNA, 19 hub genes, nine key miRNA and four key lncRNAs were identified by expression and survival analysis. Ultimately, the coexpression analysis identified RRM2-let-7a-5p- SNHG16/ MAL2 as key ceRNA subnetwork associated with prognosis of breast cancer. Conclusion: We successfully constructed a novel ceRNA network, among which each component was significantly associated with breast cancer prognosis.


2021 ◽  
Vol 12 ◽  
Author(s):  
Weimin Wang ◽  
Chunhui Lyu ◽  
Fei Wang ◽  
Congcong Wang ◽  
Feifei Wu ◽  
...  

ObjectiveAcute lymphoblastic leukemia (ALL) is a malignant disease most commonly diagnosed in adolescents and young adults. This study aimed to explore potential signatures and their functions for ALL.MethodsDifferentially expressed mRNAs (DEmRNAs) and differentially expressed long non-coding RNAs (DElncRNAs) were identified for ALL from The Cancer Genome Atlas (TCGA) and normal control from Genotype-Tissue Expression (GTEx). DElncRNA–microRNA (miRNA) and miRNA–DEmRNA pairs were predicted using online databases. Then, a competing endogenous RNA (ceRNA) network was constructed. Functional enrichment analysis of DEmRNAs in the ceRNA network was performed. Protein–protein interaction (PPI) network was then constructed. Hub genes were identified. DElncRNAs in the ceRNA network were validated using Real-time qPCR.ResultsA total of 2,903 up- and 3,228 downregulated mRNAs and 469 up- and 286 downregulated lncRNAs were identified for ALL. A ceRNA network was constructed for ALL, consisting of 845 lncRNA-miRNA and 395 miRNA–mRNA pairs. These DEmRNAs in the ceRNA network were mainly enriched in ALL-related biological processes and pathways. Ten hub genes were identified, including SMAD3, SMAD7, SMAD5, ZFYVE9, FKBP1A, FZD6, FZD7, LRP6, WNT1, and SFRP1. According to Real-time qPCR, eight lncRNAs including ATP11A-AS1, ITPK1-AS1, ANO1-AS2, CRNDE, MALAT1, CACNA1C-IT3, PWRN1, and WT1-AS were significantly upregulated in ALL bone marrow samples compared to normal samples.ConclusionOur results showed the lncRNA expression profiles and constructed ceRNA network in ALL. Furthermore, eight lncRNAs including ATP11A-AS1, ITPK1-AS1, ANO1-AS2, CRNDE, MALAT1, CACNA1C-IT3, PWRN1, and WT1-AS were identified. These results could provide a novel insight into the study of ALL.


2020 ◽  
Author(s):  
Yingtong Wu ◽  
Ning Chang ◽  
Yong Zhang ◽  
Xinxin Zhang ◽  
Leidi Xu ◽  
...  

Abstract BackgroundFBXW7 m6A modification plays an important role in lung adenocarcinoma (LUAD) progression; however, the underlying mechanisms remain unclear.MethodsThe correlation between FBXW7 and various genes related to m6A modification was analyzed using The Cancer Genome Atlas database. The regulatory effects of METTL3 on FBXW7 mRNA m6A modification were examined in a cell model, and the underlying mechanism was determined by methylated RNA immunoprecipitation, RNA immunoprecipitation, luciferase reporter, and mutagenesis assays. In vitro experiments were performed to further explore the biological effects of METTL3-mediated FBXW7 m6A modification on LUAD development.ResultsDecreased FBXW7 expression was accompanied by downregulated METTL3 expression in human LUAD tissues and was associated with a worse prognosis for LUAD in The Cancer Genome Atlas database. m6A was highly enriched in METTL3-mediated FBXW7 transcripts, and increased m6A modification in the coding sequence region increased its translation. Functionally, METTL3 overexpression or knockdown affected the apoptosis and proliferation phenotype of LUAD cells by regulating FBXW7 m6A modification and expression. Furthermore, FBXW7 overexpression in METTL3-depleted cells partially restored the suppression of LUAD cells in vitro and in vivo.ConclusionsOur findings reveal that METTL3 positively regulates FBXW7 expression and confirm the tumor-suppressive role of m6A-modified FBXW7, thus providing insight into its epigenetic regulatory mechanisms in LUAD initiation and development.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Zhizheng Liu ◽  
Hongliang Meng ◽  
Miaoxian Fang ◽  
Wenlong Guo

Background. Lower-grade glioma is an intracranial cancer that may develop into glioblastoma with high mortality. The main objective of our study is to develop microRNA for LGG patients which will provide novel prognostic biomarkers along with therapeutic targets. Methods. Clinicopathological data of LGG patients and their RNA expression profile were downloaded through The Cancer Genome Atlas Relevant expression profiles of RNA, and clinicopathological data of the LGG patients had been extracted from the database of “The Cancer Genome Atlas.” Differential expression analysis had been conducted for identification of the differentially expressed microRNAs as well as mRNAs in LGG samples and normal ones. ROC curves and K–M plots were plotted to confirm performance and for predictive accuracy. For the confirmation of microRNAs as an independent prognostic factor, an independent prognosis analysis was conducted. Moreover, target differentially expressed genes of these identified prognostic microRNAs that were extracted and protein-protein interaction networks were developed. Moreover, the biological functions of signature were determined through Genome Ontology analysis, genome pathway analysis, and Kyoto Encyclopedia of Genes. Results. 7-microRNA signature was identified that has the ability of categorization of individuals with LGG into high- and low-risk groups on the basis of significant difference in survival during training and testing cohorts (P < 0.001). The 7-microRNA signature had appeared to be robust in predictive accuracy (all AUC> 0.65). It was also approved with multivariate Cox regression along with some traditional clinical practices that we can use 7-microRNA signature for therapeutic purposes as a self-regulating predictive OS factor (P < 0.001). KEGG and Gene Ontology (GO) analyses reported that 7-microRNAs had mainly developed in important pathways related with glioma, e.g., the “cAMP signaling pathway,” “glutamatergic synapses,” and “calcium signaling pathway”. Conclusion. A newly discovered 7-microRNA signature could be a potential target for the diagnosis and treatment for LGG patients.


Sign in / Sign up

Export Citation Format

Share Document