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. 2020 Jan-Dec:19:1533033820930119.
doi: 10.1177/1533033820930119.

Integrated Profiling Revealed Potential Regulatory Networks Among Long Noncoding RNAs and mRNAs in Mucosal Gastric Cancer

Ke-Kang Sun  1 , Xiao-Jun Shen  1 , Dong Yang  1 , Yang Jiao  2 , Xiao-Yang Wu  1
Affiliations

Integrated Profiling Revealed Potential Regulatory Networks Among Long Noncoding RNAs and mRNAs in Mucosal Gastric Cancer

Ke-Kang Sun et al. Technol Cancer Res Treat. 2020 Jan-Dec.

Abstract

Gastric cancer is one of the most commonly occurring cancers worldwide. Investigation of long noncoding RNAs is of increasing interest, particularly in relation to their contribution to progression and prognosis of gastric cancers; however, insufficient studies been performed investigating the part of long noncoding RNAs play in gastric cancer carcinogenesis. Patterns of dysregulated long noncoding RNA and messenger RNA between mucosa gastric cancer and adjacent normal tissues were identified using long noncoding RNAs microarray analysis. Quantitative real-time polymerase chain reaction was conducted as a means to verify the obtained data. Both Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were subsequently used to investigate the function of dysregulated long noncoding RNAs and messenger RNAs. Cis and trans action was used to predict the possible targets of long noncoding RNAs, and a coexpression network was created to simulate the complex intergenic interactions. Ninety-five dysregulated long noncoding RNAs and 123 messenger RNAs were identified, and quantitative real-time polymerase chain reaction was used to validate 6 filtered long noncoding RNAs. Gene Ontology and KEGG pathway analyses identified several remarkably biological processes and signaling pathways, including spliceosome, RNA transport, and ubiquitin-mediated proteolysis. The transcriptional factors MYC, GABPA, and E2F1 were found to play a central function in the long noncoding RNAs process, as indicated by the coexpression network. This study revealed the dysregulated long noncoding RNA profiles of mucosal gastric cancer. The results shed light on the biological function of long noncoding RNAs in gastric cancer pathogenesis. This provides useful information for exploring potential early screening biomarkers in gastric cancer.

Keywords: expression profiles; long noncoding RNA (lncRNA); mucosal gastric cancer.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
A, Hierarchical clustering and a heat map of the lncRNA profile comparison between mucosa gastric cancer and adjacent normal tissues. N represents normal tissue and T represents gastric cancer tissue. B, Chromosomal locations of dysregulated lncRNA and messenger RNAs.
Figure 2.
Figure 2.
Gene Ontology (GO) and KEGG pathway analyses of dysregulated lncRNAs between mucosa gastric cancer and adjacent normal tissues. The top 20 GO terms for the dysregulated lncRNAs in each domain: (A) biological process; (B) cellular component; (C) molecular function. (D) The top 20 KEGG terms for dysregulated lncRNAs in mucosa gastric cancer tissues. The annotation terms are displayed on the vertical axis, and the number of genes annotated to the term is represented on the horizontal axis.
Figure 3.
Figure 3.
Gene Ontology (GO) and KEGG pathway analyses of dysregulated messenger RNAS (mRNAs) between mucosa gastric cancer and adjacent normal tissues. A, The 10 highest GO terms in each domain for dysregulated mRNAs in mucosa gastric cancer. B, The top 30 KEGG terms for dysregulated mRNAs in mucosa gastric cancer.
Figure 4.
Figure 4.
Fine mapping for the coexpression of lncRNAs and coding genes. The genomic position is identified by an abscissa, a red arrow indicates the genomic position of mRNA transcripts, and a blue arrow represents the location of the lncRNA. An ordinate signifies the correlation coefficient between lncRNA and mRNA transcript. A, Coexpression of ENST00000497228 and coding gene FMO4. B, Co-expression of ENST00000592710 and coding gene CYP4F2. CYP4F2 indicates cytochrome P450, family 4, subfamily F, polypeptide 2.
Figure 5.
Figure 5.
The transcriptional factor profiling of the top results based on aberrantly expressed lncRNAs in mucosa gastric cancer tissues.
Figure 6.
Figure 6.
Transcription factors (TFs)-lncRNA-mRNA networks. Green, red, and blue nodes represent mRNAs, lncRNAs, and TFs, respectively.
Figure 7.
Figure 7.
The validation of 6 dysregulated lncRNAs by qRT-PCR. The relative expression levels of lncRNA in 10 pairs of mucosa gastric cancer and adjacent normal tissues. *P < .05. qRT-PCR indicates quantitative real-time polymerase chain reaction.
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