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Construction and Comprehensive Analyses of a Competing Endogenous RNA Network in Tumor-Node-Metastasis Stage I Hepatocellular Carcinoma.
Biomed Res Int. 2020; 2020:5831064.BR

Abstract

Background

Long noncoding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs) and interact with microRNAs (miRNAs) to regulate target gene expression, which can greatly influence tumor development and progression. Different tumor-node-metastasis (TNM) stages of hepatocellular carcinoma (HCC) defined by the American Joint Committee on Cancer (AJCC) have different clinical results. Our purpose was to comprehensively analyze differentially expressed (DE) lncRNAs, miRNAs, and mRNAs in stage I HCC and identify prognosis-associated RNAs.

Methods

RNA-seq data were obtained from The Cancer Genome Atlas (TCGA) database. A stage I HCC-associated miRNA-lncRNA-mRNA network was constructed. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses of ceRNA-associated DEmRNAs were performed using Database for Annotation, Visualization, and Integrated Discovery (DAVID) 6.8 and Clusterprofile in the R package. The protein-protein interaction (PPI) network of the above mRNAs was then constructed using STRING. Finally, the association between lncRNAs and mRNAs in the ceRNA network and prognosis of patients was further analyzed. Linear regression analysis of the above lncRNAs and mRNAs associated with overall survival was performed.

Results

After a comparison between HCC and adjacent nontumor tissues, 778 lncRNAs, 1608 mRNAs, and 102 miRNAs that were abnormally expressed were identified. The ceRNA network was composed of 56 DElncRNAs, 14 DEmiRNAs, and 30 DEmRNAs. Functional analysis results showed that 30 DEmRNAs were enriched in 14 GO biological process categories and 6 KEGG categories (false discovery rate (FDR) < 0.05). A PPI network was composed of 22 nodes and 58 edges. We detected 4 DElncRNAs (BPESC1, AC061975.6, AC079341.1, and CLLU1) and 6 DEmRNAs (CEP55, E2F1, E2F7, EZH2, G6PD, and SLC7A11) that had significant influences on the overall survival (OS) of stage I HCC patients (P < 0.05). lncRNA BPESC1 was positively correlated with mRNA CEP55 via miR-424, and lncRNA AC061975.6 was positively correlated with mRNA E2F1 via miR-519d.

Conclusion

Our study identified novel lncRNAs and mRNAs that were associated with the progression and prognosis of stage I HCC and further investigated the regulatory mechanism of lncRNA-mediated ceRNAs in the development of stage I HCC.

Authors+Show Affiliations

Department of Liver Disease, The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing 210003, China.Department of Hepatology, Infectious Diseases Hospital Affiliated with Soochow University, Suzhou 215000, China.Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.Department of Liver Disease, The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing 210003, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32104698

Citation

Gu, Xuefeng, et al. "Construction and Comprehensive Analyses of a Competing Endogenous RNA Network in Tumor-Node-Metastasis Stage I Hepatocellular Carcinoma." BioMed Research International, vol. 2020, 2020, p. 5831064.
Gu X, Li H, Sha L, et al. Construction and Comprehensive Analyses of a Competing Endogenous RNA Network in Tumor-Node-Metastasis Stage I Hepatocellular Carcinoma. Biomed Res Int. 2020;2020:5831064.
Gu, X., Li, H., Sha, L., & Zhao, W. (2020). Construction and Comprehensive Analyses of a Competing Endogenous RNA Network in Tumor-Node-Metastasis Stage I Hepatocellular Carcinoma. BioMed Research International, 2020, 5831064. https://doi.org/10.1155/2020/5831064
Gu X, et al. Construction and Comprehensive Analyses of a Competing Endogenous RNA Network in Tumor-Node-Metastasis Stage I Hepatocellular Carcinoma. Biomed Res Int. 2020;2020:5831064. PubMed PMID: 32104698.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Construction and Comprehensive Analyses of a Competing Endogenous RNA Network in Tumor-Node-Metastasis Stage I Hepatocellular Carcinoma. AU - Gu,Xuefeng, AU - Li,Hongbo, AU - Sha,Ling, AU - Zhao,Wei, Y1 - 2020/02/11/ PY - 2019/10/26/received PY - 2019/12/14/revised PY - 2019/12/26/accepted PY - 2020/2/28/entrez PY - 2020/2/28/pubmed PY - 2020/2/28/medline SP - 5831064 EP - 5831064 JF - BioMed research international JO - Biomed Res Int VL - 2020 N2 - Background: Long noncoding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs) and interact with microRNAs (miRNAs) to regulate target gene expression, which can greatly influence tumor development and progression. Different tumor-node-metastasis (TNM) stages of hepatocellular carcinoma (HCC) defined by the American Joint Committee on Cancer (AJCC) have different clinical results. Our purpose was to comprehensively analyze differentially expressed (DE) lncRNAs, miRNAs, and mRNAs in stage I HCC and identify prognosis-associated RNAs. Methods: RNA-seq data were obtained from The Cancer Genome Atlas (TCGA) database. A stage I HCC-associated miRNA-lncRNA-mRNA network was constructed. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses of ceRNA-associated DEmRNAs were performed using Database for Annotation, Visualization, and Integrated Discovery (DAVID) 6.8 and Clusterprofile in the R package. The protein-protein interaction (PPI) network of the above mRNAs was then constructed using STRING. Finally, the association between lncRNAs and mRNAs in the ceRNA network and prognosis of patients was further analyzed. Linear regression analysis of the above lncRNAs and mRNAs associated with overall survival was performed. Results: After a comparison between HCC and adjacent nontumor tissues, 778 lncRNAs, 1608 mRNAs, and 102 miRNAs that were abnormally expressed were identified. The ceRNA network was composed of 56 DElncRNAs, 14 DEmiRNAs, and 30 DEmRNAs. Functional analysis results showed that 30 DEmRNAs were enriched in 14 GO biological process categories and 6 KEGG categories (false discovery rate (FDR) < 0.05). A PPI network was composed of 22 nodes and 58 edges. We detected 4 DElncRNAs (BPESC1, AC061975.6, AC079341.1, and CLLU1) and 6 DEmRNAs (CEP55, E2F1, E2F7, EZH2, G6PD, and SLC7A11) that had significant influences on the overall survival (OS) of stage I HCC patients (P < 0.05). lncRNA BPESC1 was positively correlated with mRNA CEP55 via miR-424, and lncRNA AC061975.6 was positively correlated with mRNA E2F1 via miR-519d. Conclusion: Our study identified novel lncRNAs and mRNAs that were associated with the progression and prognosis of stage I HCC and further investigated the regulatory mechanism of lncRNA-mediated ceRNAs in the development of stage I HCC. SN - 2314-6141 UR - https://www.unboundmedicine.com/medline/citation/32104698/Construction_and_Comprehensive_Analyses_of_a_Competing_Endogenous_RNA_Network_in_Tumor_Node_Metastasis_Stage_I_Hepatocellular_Carcinoma_ L2 - https://doi.org/10.1155/2020/5831064 DB - PRIME DP - Unbound Medicine ER -
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