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. 2019 Jul;8(8):3875-3891.
doi: 10.1002/cam4.2236. Epub 2019 May 22.

Screening key lncRNAs for human rectal adenocarcinoma based on lncRNA-mRNA functional synergistic network

Xiongwen Zhu  1 , Dongguo Wang  2 , Qianyuan Lin  3 , Guiyang Wu  1 , Shichao Yuan  1 , Fubo Ye  1 , Qinghao Fan  1
Affiliations

Screening key lncRNAs for human rectal adenocarcinoma based on lncRNA-mRNA functional synergistic network

Xiongwen Zhu et al. Cancer Med. 2019 Jul.

Abstract

Background: Rectal adenocarcinoma (READ) is one of the deadliest malignancies, and the molecular mechanisms underlying the initiation and development of READ remain largely unknown. In this study, we aimed to find key long noncoding RNAs (lncRNAs) and mRNAs in READ by RNA sequencing.

Methods: RNA sequencing was performed to identify differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) between READ and normal tissue. READ-specific protein-protein interaction (PPI), DElncRNA-DEmRNA coexpression, and DElncRNA-nearby DEmRNA interaction networks were constructed. DEmRNAs and DEmRNAs coexpressed with DElncRNAs were functionally annotated.

Results: A total of 2113 DEmRNAs and 150 DElncRNAs between READ and normal tissue were identified. The PPI network identified several hub proteins, including CDK1, AURKB, CDC6, FOXQ1, NUF2, and TOP2A. The DElncRNA-DEmRNA coexpression and DElncRNA-nearby DEmRNA interaction networks identified some hub lncRNAs, including CCAT1, LOC105374879, GAS5, and B3GALT5-AS1. The colorectal cancer pathway, the intestinal immune network for IgA production and the p53 signaling pathway were three pathways significantly enriched in DEmRNAs and DEmRNAs coexpressed with DElncRNAs. MSH6 coexpressed with two DElncRNAs (LOC105374879 and CASC15) and BCL2 coexpressed with B3GALT5-AS1 were significantly enriched in the colorectal cancer signaling pathway. TNFRSF17 coexpressed with B3GALT5-AS1 was enriched in the intestinal immune network for IgA production. CCNB2 coexpressed with LOC105374879 was enriched in the p53 signaling pathway.

Conclusion: A total of four DEmRNAs (MSH6, BCL2, TNFRSF17, and CCNB2) and three DElncRNAs (LOC105374879, CASC15, and B3GALT5-AS1) may be involved in the pathogenesis of READ; this data may contribute to understanding the mechanisms of READ and the development of therapeutic strategies for READ.

Keywords: DElncRNA-DEmRNA coexpression; DElncRNAs; DEmRNAs; RNA sequencing; rectal adenocarcinoma.

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Conflict of interest statement

The authors declare that they have no conflict of interest. No competing financial interests exist.

Figures

Figure 1
Figure 1
Heat map of the top 100 DEmRNAs and all of DElncRNAs between READ and normal tissues. (A) DEmRNAs. (B) DElncRNAs. Rows and columns represent DElncRNAs/DEmRNAs and tissue samples, respectively. The color scale indicates expression levels. (C) Circos plots representing the distribution of DElncRNAs and DEmRNAs on chromosomes. The outer layer cycle is the chromosome map of the human genome. The inner layers represent the distribution of DEmRNAs and DElncRNAs on different chromosomes, respectively. Red and blue colors represent up‐ and downregulation, respectively
Figure 2
Figure 2
The top 15 significantly enriched GO terms and KEGG pathways for DEmRNAs in READ. The x‐axis shows ‐log FDR, and the y‐axis shows GO terms or KEGG pathways. (A) Biological process. (B) Cellular component. (C) Molecular function. (D) KEGG pathways
Figure 3
Figure 3
READ‐specific PPI network. Ellipses are used to represent nodes, and lines are used to represent edges. Red and blue represent up‐ and downward adjustments, respectively. The black border indicates the top 10 up‐ and downregulated proteins
Figure 4
Figure 4
Positively coexpressed DElncRNA‐DEmRNA network. Ellipses and inverted triangles represent DEmRNAs and DElncRNAs, respectively. Red and blue colors represent up‐ and downregulation, respectively. The black border indicates the top 10 up‐ and downregulated DElncRNAs and DEmRNAs
Figure 5
Figure 5
Negatively coexpressed DElncRNA‐DEmRNA network. Ellipses and inverted triangles represent DEmRNAs and DElncRNAs, respectively. Red and blue colors represent up‐ and downregulation, respectively. The black border indicates the top 10 up‐ and downregulated DElncRNAs and DEmRNAs
Figure 6
Figure 6
Top 15 significantly enriched GO terms and KEGG pathways for DEmRNAs coexpressed with DElncRNAs in READ. The x‐axis shows ‐log FDR, and the y‐axis shows GO terms or KEGG pathways. (A) Biological process. (B) Cellular component. (C) Molecular function. (D) KEGG pathways
Figure 7
Figure 7
READ pathways (p53 signaling pathway, intestinal immune network for IgA production, and colorectal cancer pathway) enriched in DEmRNAs during READ. The red and green rectangles represent components regulated by DEmRNAs that are enriched in READ
Figure 8
Figure 8
DElncRNA‐nearby DEmRNA interaction network in READ. (A) DElncRNA‐nearby DEmRNA interaction network. (B) Interaction network showing the overlap of the DElncRNA‐DEmRNA coexpression network with the DElncRNA‐nearby DEmRNA interaction network. Ellipses and inverted triangles represent DEmRNAs and DElncRNAs, respectively. Red and blue colors represent up‐ and downregulation, respectively. The black border indicates the top 10 up‐ and downregulated
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