Identification of key microRNAs and hub genes in non‐small‐cell lung cancer using integrative bioinformatics and functional analyses

Abstract

Non-small-cell lung cancer (NSCLC) is an extremely debilitating respiratory malignancy. However, the pathogenesis of NSCLC has not been fully clarified.The main objective of our study was to identify potential microRNAs (miRNAs) and their regulatory mechanism in NSCLC. Using a systematic review, two NSCLC-associated miRNA data sets (GSE102286 and GSE56036) were obtained from Gene Expression Omnibus, and the differentially expressed miRNAs (DE-miRNAs) were accessed by GEO2R. Survival analysis of candidate DE-miRNAs was conducted using the Kaplan-Meier plotter database. To further illustrate the roles of DE-miRNAs in NSCLC, their potential target genes were predicted by miRNet and were annotated by the Database for Annotation, Visualization and Integrated Discovery (DAVID) program. Moreover, the protein-protein interaction (PPI) and miRNA-hub gene regulatory network were established using the STRING database and Cytoscape software. The function of DE-miRNAs in NSCLC cells was evaluated by transwell assay. Compared with normal tissues, a total of eight DE-miRNAs was commonly changed in two data sets. The survival analysis showed that six miRNAs (miR-21-5p, miR-31-5p, miR-708-5p, miR-30a-5p, miR-451a, and miR-126-3p) were significantly correlated with overall survival. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that target genes of upregulated miRNAs were enriched in pathways in cancer, microRNAs in cancer and proteoglycans in cancer, while the target genes of downregulated miRNAs were mainly associated with pathways in cancer, the PI3K-Akt signaling pathway and HTLV-I infection. Based on the miRNA-hub gene network and expression analysis, PTEN, EGFR, STAT3, RHOA, VEGFA, TP53, CTNNB1, and KRAS were identified as potential target genes. Furthermore, all six miRNAs exhibited significant effects on NSCLC cell invasion. These findings indicate that six DE-miRNAs and their target genes may play important roles in the pathogenesis of NSCLC, which will provide novel information for NSCLC treatments.

MicroRNA‑126: A new and promising player in lung cancer (Review)

“…Recently, Chen et al (18) demonstrated that silencing miR-126 could reverse the anticancer effects of naringin on NSCLC cell growth, in which naringin induces a reduction in the phosphatidylinositol-3 protein kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin and suppresses vascular cell adhesion molecule 1 protein levels. In addition, miR-126 exhibits a suppressive effect on NSCLC cell invasion by interacting with three hub genes: VEGFA, AKT1, and Kirsten rat sarcoma viral oncogene homologue (19). Additionally, other studies have demonstrated that miR-126 can suppress the growth, migration and invasion of NSCLC cells by targeting chemokine (C-C motif) receptor 1 and solute carrier family 7 (cationic amino acid transporter, y+ system) member 5 (SLC7A5) or v-crk sarcoma virus CT10 oncogene homologue (Crk) (20)(21)(22)(23), indicating that miR-126 may control the growth of lung cancer cells through multiple targets (Table Ⅰ).…”

“…In the past decade, a large number of studies have documented that miR-126 may also be a meaningful prognostic marker of lung cancer (19,21,(63)(64)(65) (Table II). Recently, Xu et al (66) found that high plasma expression level of miR-126 in patients with lung cancer was associated with shorter disease-free survival [hazard ratios (HRs) of univariate Cox and multivariate Cox were 1.867 and 1.582, respectively; 95% confidence intervals (CIs) of univariate Cox and multivariate Cox were 1.386-2.515 and 1.158-2.161, respectively] and overall survival (OS) (HRs of univariate Cox and multivariate Cox were 1.706 and 1.320, respectively; 95% CIs of univariate Cox and multivariate Cox were 1.218-2.388 and 0.932-1.817, respectively).…”

Propofol suppresses the progression of non‑small cell lung cancer via downregulation of the miR‑21‑5p/MAPK10 axis

“…Propofol also inhibits the progression of NSCLC by regulating the expression level of some miRNAs, including miR-372 (13), miR-1284 (14) and miR-486 (15). As an important oncogene in NSCLC, a higher miR-21-5p level is associated with recurrence (38), tumor stage (39) and poor overall survival (40) of patients with NSCLC. The link between Fpropofol and miR-21 has been reported in several diseases, but not in NSCLC.…”

High miR-31-5p expression promotes colon adenocarcinoma progression by targeting TNS1

“…Using bioinformatic analysis, miRNAs that exhibit oncogenic activity in carcinogenesis have been identified, including miR-21 [10], miR-155 [11], and miR-142 [12]. Literature indicates that miR-31-5p is overexpressed in diverse tumor types [13], and studies have explored its role in lung and breast cancer AGING metastasis [14,15]. However, the underlying mechanisms of the role of miR-31-5p in COAD remain unknown.…”