Abstract
BackgroundThe present study is to screen lymph node metastasis-related microRNAs (miRNAs) in lung adenocarcinoma (LUAD) and uncover their underlying mechanisms.MethodsThe miRNA microarray dataset was collected from the Gene Expression Omnibus database under accession number GSE64859. The differentially expressed miRNAs (DEMs) were identified using a t-test. Target genes of DEMs were predicted through the miRWalk2.0 database. The function of these target genes was annotated with the clusterProfiler and the Database for Annotation, Visualization and Integrated Discovery (DAVID) tools. Protein-protein interaction network was established using the STRING database to extract hub target genes. The expressions and associations with survival and lymph node metastasis of miRNAs and target genes were validated by analysis of The Cancer Genome Atlas (TCGA) dataset.ResultsEight DEMs were identified between lymph node metastasis and non-metastasis samples of GSE64859 dataset. miRNA-target gene pairs were predicted between six DEMs and 251 target genes (i.e. hsa-miR-224-PRPF4B, hsa-miR-147b-WDR82 and hsa-miR-31-NR3C2). The clusterProfiler analysis showed WDR82 was involved in the mRNA surveillance pathway, while the GO enrichment analysis using the DAVID database indicated PRPF4B participated in the protein phosphorylation and NR3C2 was related with the transcription, DNA-templated. WDR82 and PRPF4B may be hub genes because they could interact with others. Two DEMs (miR-31-5p and miR-31-3p) and 45 target genes (including PRPF4B and NR3C2) were significantly associated with overall survival. The expressions of miR-224 and miR-147b were validated to be upregulated, while WDR82, PRPF4B and NR3C2 were downregulated in lymph node metastasis samples of TCGA datasets compared with non-metastasis samples. Also, there were significantly negative expression correlations between miR-147b and WDR82, between miR-224 and PRPF4B, as well as between miR-31 and NR3C2 in LUAD samples.ConclusionsThe present study identified several crucial miRNA-mRNA interaction pairs, which may provide novel explanations for the lymph node metastasis and poor prognosis for LUAD patients.
Highlights
Lung cancer is the leading cause of cancer-related death worldwide, with the number of deaths estimated up to three million by 2035 (Didkowska et al, 2016)
Analysis of miRNA expression profiles in lung adenocarcinoma (LUAD) tissues from patients with lymph node metastasis compared to those without lymph node metastasis identified a total of 8 differentially expressed miRNAs (DEMs) (Table 1)
Based on the given threshold value, a total of 259 miRNA–target gene interaction pairs were predicted, including 6 DEMs and 251 target genes, which were used for constructing the miRNA–target regulatory network (Table S1; Fig. 3)
Summary
Lung cancer is the leading cause of cancer-related death worldwide, with the number of deaths estimated up to three million by 2035 (Didkowska et al, 2016). The present study is to screen lymph node metastasis-related microRNAs (miRNAs) in lung adenocarcinoma (LUAD) and uncover their underlying mechanisms. The expressions and associations with survival and lymph node metastasis of miRNAs and target genes were validated by analysis of The Cancer Genome Atlas (TCGA) dataset. Two DEMs (miR-31-5p and miR31-3p) and 45 target genes (including PRPF4B and NR3C2) were significantly associated with overall survival. The expressions of miR-224 and miR-147b were validated to be upregulated, while WDR82, PRPF4B and NR3C2 were downregulated in lymph node metastasis samples of TCGA datasets compared with non-metastasis samples. The present study identified several crucial miRNA-mRNA interaction pairs, which may provide novel explanations for the lymph node metastasis and poor prognosis for LUAD patients
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