Microarray Expression Profile of Long Non-coding RNAs in Paclitaxel-resistant Human Lung Adenocarcinoma Cells

Paclitaxel (PTX)-based chemotherapy is a standard treatment for human lung adenocarcinoma, but treatment often fails since resistance develops. Recent studies have described the activity of long non-coding RNAs (lncRNAs) in many biological processes and human diseases. Chemotherapy resistance is one of these areas, but the role of lncRNAs in paclitaxel resistance of human lung adenocarcinoma cells has not been reported. A paclitaxel resistance model was established using A549 human lung adenocarcinoma cells. lncRNAs and mRNAs were profiled in parental A549 and paclitaxel-resistant A549/PTX cells by microarray analysis. Real-time quantitative PCR (RT-qPCR) was used to validate the results of the microarray. Chromosomal distribution patterns of differentially expressed lncRNAs and mRNAs were assessed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using gene set enrichment. We screened 1,154 lncRNAs and 1,733 mRNAs that had a >3-fold difference in expression in A549/PTX cells compared with A549 cells, most of which were downregulated. Nine lncRNAs and six mRNAs were randomly selected and validated by RT-qPCR. Most aberrantly expressed lncRNAs and mRNAs were located on chromosomes 1, 2, 6, 12 and 17, particularly on chromosome 1. Bioinformatics, GO and KEGG pathway analyses, revealed that some differentially expressed genes regulated classical functions and pathways such as cytosol components, protein binding, gene expression and metabolic pathways. Differential expression of lncRNAs and mRNAs in A549/PTX and A549 cells indicates that various lncRNAs may be useful diagnostic or prognostic markers of resistance to treatment, or future targets for paclitaxel-based chemotherapy, providing a novel rationale for clinical treatment.