Construction of a competing endogenous RNA network using differentially expressed lncRNAs, miRNAs and mRNAs in non-small cell lung cancer

The competing endogenous RNA (ceRNA) network is crucial for the development and progression of tumors, including non-small cell lung cancer (NSCLC). However, what type of ceRNA network regulates NSCLC has not been clarified. The present study aimed to elucidate the long non-coding RNA (lncRNA)/microRNA (miRNA)/mRNA ceRNA network in NSCLC, particularly for the significance of lncRNAs in NSCLC. NSCLC-specific differentially expressed lncRNAs, miRNAs and mRNAs in the Cancer Genome Atlas (TCGA) were analyzed and their relationship was analyzed by a ceRNA network. Their potential functions of differentially expressed mRNAs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Furthermore, the expression levels of four selected lncRNAs in TCGA were determined and their associated survival of patients was examined. In addition, the expression profiles of these four lncRNAs in 48 NSCLC specimens and cell lines, their cellular distribution and associated clinical parameters were examined. We successfully constructed a ceRNA network, including 113 lncRNAs, 12 miRNAs and 36 mRNAs differentially expressed between NSCLC and non-tumor tissues. LINC00525, MED4-AS1, STEAP2-AS1 and SYNPR-AS1 lncRNAs were selected and validated for their association with the survival of NSCLC patients. The expression of these lncRNAs was upregulated in 48 NSCLC tissues and was varying in NSCLC cells. While LINC00525 was mainly expressed in the cytoplasm, MED4-AS1 was in both the nucleus and cytoplasm of A549 cells. In addition, the expression of LINC00525 was significantly associated with smoking history (P<0.05); MED4-AS1 was significantly associated with women, poor differentiation and lymph node metastasis (P<0.05); STEAP2-AS1 was significantly associated with women (P<0.01); and SYNPR-AS1 was significantly associated with women and adenocarcinoma (P<0.05). These lncRNAs may be valuable biomarkers for prognosis of NSCLC and the ceRNA network may provide new insights in the pathogenesis of NSCLC.