Background The present study is to screen lymph node metastasis-related microRNAs (miRNAs) in lung adenocarcinoma (LUAD) and uncover their underlying mechanisms. Methods The 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. Results Eight 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. Conclusions 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.

Abstract. The aim of the present study was to identify more effective molecular diagnostic biomarkers for esophageal squamous cell carcinoma (ESCC). The non-coding RNA profile GSE43732, generated from 238 paired frozen tissues from 119 patients, was analyzed. Raw data were preprocessed and the differentially expressed miRNAs were screened by limma package with log 2 fold change >2. Prognosis-associated miRNAs were identified using receiver operating characteristic (ROC) and Kaplan-Meier (KM) curve analysis. miRNAs with an area under the ROC curve of ≥0.7 were selected. miRNA target genes were identified from verification and predictive databases, and an miRNA regulatory network was constructed and visualized using Cytoscape software. Gene Ontology and pathway enrichment analyses of the target genes were performed using TargetMine. A total of 107 differentially expressed miRNAs, including 54 upregulated and 53 downregulated miRNAs, were obtained. The KM survival curves revealed that 44 miRNAs were significantly associated with prognosis. Furthermore, 9 upregulated and 3 downregulated miRNAs were obtained. Two upregulated miRNAs, hsa-miR-143-3p and hsa-miR-145-5p, and two downregulated miRNAs, hsa-miR-182-5p and hsa-miR-455-5p, were identified and demonstrated to be associated with prognosis in ESCC. In addition, 8 known and 245 predicted target genes of hsa-miR-455-5p were screened and the regulatory networks were constructed. Furthermore, these genes were functionally associated with macromolecule metabolic process and melanoma. In conclusion, two novel tumor suppressive miRNAs including miR-182-5p and miR-455-5p were identified. miR-455-5p in particular may be involved in the regulation of ESCC. These miRNAs may be used to predict the prognosis of ESCC.

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