Abstract
BackgroundLung adenocarcinoma (LUAD) is a common lung cancer with a high mortality, for which microRNAs (miRNAs) play a vital role in its regulation. Multiple messenger RNAs (mRNAs) may be regulated by miRNAs, involved in LUAD tumorigenesis and progression. However, the miRNA–mRNA regulatory network involved in LUAD has not been fully elucidated.MethodsDifferentially expressed miRNAs and mRNA were derived from the Cancer Genome Atlas (TCGA) dataset in tissue samples and from our microarray data in plasma (GSE151963). Then, common differentially expressed (Co-DE) miRNAs were obtained through intersected analyses between the above two datasets. An overlap was applied to confirm the Co-DEmRNAs identified both in targeted mRNAs and DEmRNAs in TCGA. A miRNA–mRNA regulatory network was constructed using Cytoscape. The top five miRNA were identified as hub miRNA by degrees in the network. The functions and signaling pathways associated with the hub miRNA-targeted genes were revealed through Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The key mRNAs in the protein–protein interaction (PPI) network were identified using the STRING database and CytoHubba. Survival analyses were performed using Gene Expression Profiling Interactive Analysis (GEPIA).ResultsThe miRNA–mRNA regulatory network consists of 19 Co-DEmiRNAs and 760 Co-DEmRNAs. The five miRNAs (miR-539-5p, miR-656-3p, miR-2110, let-7b-5p, and miR-92b-3p) in the network were identified as hub miRNAs by degrees (>100). The 677 Co-DEmRNAs were targeted mRNAs from the five hub miRNAs, showing the roles in the functional analyses of the GO analysis and KEGG pathways (inclusion criteria: 836 and 48, respectively). The PPI network and Cytoscape analyses revealed that the top ten key mRNAs were NOTCH1, MMP2, IGF1, KDR, SPP1, FLT1, HGF, TEK, ANGPT1, and PDGFB. SPP1 and HGF emerged as hub genes through survival analysis. A high SPP1 expression indicated a poor survival, whereas HGF positively associated with survival outcomes in LUAD.ConclusionThis study investigated a miRNA–mRNA regulatory network associated with LUAD, exploring the hub miRNAs and potential functions of mRNA in the network. These findings contribute to identify new prognostic markers and therapeutic targets for LUAD patients in clinical settings.
Highlights
Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer, accounting for approximately 40% of all cases of lung cancer in China and other countries (Bray et al, 2018; Cao and Chen, 2019; Siegel et al, 2020)
The miRNA–messenger RNA (mRNA) regulatory network is characterized in such a way that individual miRNA could regulate a wealth of different mRNAs of genes, and the individual mRNA of a target gene could be correspondingly suppressed by multiple different miRNAs (Cui et al, 2020; Li et al, 2020; Liu et al, 2020)
It is necessary to examine the miRNA–mRNA regulatory network in LUAD to advance our understanding of its molecular mechanisms
Summary
Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer, accounting for approximately 40% of all cases of lung cancer in China and other countries (Bray et al, 2018; Cao and Chen, 2019; Siegel et al, 2020). LUAD is characterized by rapid progression and early development of metastases and a high recurrence rate, with the highest morbidity and mortality in both genders (Bray et al, 2018; Cao and Chen, 2019; Siegel et al, 2020). The overall 5-year survival rates for LUAD only reach approximately 20% (Bray et al, 2018; Miller et al, 2019) given the lack of early detection and limited effective therapies at earlier stages of disease (Gan et al, 2017). It is necessary to examine the miRNA–mRNA regulatory network in LUAD to advance our understanding of its molecular mechanisms
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