Lung squamous cell carcinoma (LUSC) accounts for a significant proportion of lung cancer and there have been few therapeutic alternatives for recurrent LUSC due to the lack of specific driver molecules. To investigate the prospective role of lncRNAs in the tumorigenesis and progression of LUSC, the aberrantly expressed lncRNAs were calculated based on The Cancer Genome Atlas RNA-seq data. Of 7589 lncRNAs with 504 LUSC cases, 884 lncRNAs were identified as being aberrantly expressed (|log2 fold change| >2 and adjusted P<0.05) by DESeq R. The top 10 lncRNAs with the highest diagnostic value were SFTA1P,LINC00968, LINC00961, LINC01572,RP1-78O14.1, FENDRR, LINC01314,LINC01272, GATA6-AS1, and MIR3945HG. In addition to the significant roles in the carcinogenesis of LUSC, several lncRNAs also played vital parts in the survival and progression of LUSC. SFTA1P, LINC01272, GATA6-AS1 and MIR3945HG were closely related to the survival time of LUSC. Furthermore, LINC01572 and LINC01314 could distinguish the LUSC at early stage from that at advanced stage. The prospective molecular assessment of key lncRNAs showed that a certain series of genes could be involved in the regulation network. Furthermore, the OncoPrint from cBioPortal indicated that 14% (69/501) LUSC cases with genetic alterations could be obtained, including amplification, deep deletion and mRNA upregulation. More interestingly, the cases with genetic alterations had a poorer survival as compared to those without alterations. Overall, the study propounds a potentiality for interpreting the pathogenesis and development of LUSC with lncRNAs, and provides a novel platform for searching for more capable diagnostic biomarkers for LUSC.

Accumulating evidence suggests that the dysregulation of long non-coding RNAs (lncRNAs) serves vital roles in the incidence and progression of lung cancer. However, the molecular mechanisms of LINC00968, a recently identified lncRNA, remain unknown. The objective of present study was to investigate the role of a prospective lncRNA-miRNA‑mRNA network regulated by LINC00968 in non-small cell lung cancer cells. Following the transfection of lentiviruses carrying LINC00968 into A549 cells, the microRNA (miRNA) expression profile of the cells in response to the overexpression of LINC00968 was detected using an miRNA microarray. Five differentially expressed miRNAs (DEMs) with LINC00968 overexpression were obtained, including miR-9-3p, miR‑22-5p, miR-668-3p, miR‑3675-3p and miR-4536-3p. Five target prediction algorithms and three target validation algorithms were used to obtain 1,888 prospective target genes of the five DEMs. The result of Gene Ontology analysis suggested that these five DEMs were involved in complex cellular pathways, which included intracellular transport, organelle lumen and nucleotide binding. Furthermore, analysis of Kyoto Encyclopedia of Genes and Genomes pathways indicated that the five DEMs were important regulators in the adherens junction and focal adhesion. An lncRNA-miRNA-mRNA regulatory network and a protein-protein interaction network were then constructed. Eventually, a prospective lncRNA‑miRNA-mRNA regulatory network of LINC00968, three miRNAs (miR-9, miR-22 and miR-4536) and two genes (polo-like kinase 1 and exportin-1) was obtained following validation in the Cancer Genome Atlas database. These results may provide novel insights to support future research into lncRNA in lung cancer.

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