Objective: The aim of this study was to investigate the molecular mechanisms underlying
cisplatin (DDP) resistance in
non-small cell lung cancer (NSCLC) cells by constructing a
competing endogenous RNA (
ceRNA) network. Methods: The gene expression profiles of human
lung adenocarcinoma DDP-resistant cell line (A549/DDP) and its progenitor (A549) were comparatively evaluated by whole-transcriptome sequencing. The differentially expressed genes (DEGs) were subjected to KEGG pathway analysis. The expression levels of mRNAs involved in several pathways associated with conferring DDP resistance to
tumor cells were evaluated. The
ceRNA network was constructed based on the
mRNA expression levels and the sequencing data of
miRNA and
lncRNA. Several
ceRNA regulatory relationships were validated. Results: We quantified the expression of 17 genes involved in the six pathways by quantitative real-time polymerase chain reaction (qRT-PCR). The differential
protein expression levels of eight genes were quantified by western blotting. Western blot analysis revealed six differentially expressed
proteins (MGST1, MGST3, ABCG2, FXYD2, ALDH3A1, and GST-ω1). Among the genes encoding these six
proteins, ABCG2, ALDH3A1, MGST3, and FXYD2 exhibited interaction with 8 lncRNAs and 4
miRNAs in the
ceRNA regulatory network. The expression levels of these lncRNAs and
miRNAs were quantified in cells; among these, 6 lncRNAs and 4
miRNAs exhibited differential expression between A549/DDP and A549 groups, which were used to construct a
ceRNA network. The
ceRNA regulatory network of MSTRG51053.2-miR-432-5p-MGST3 was validated by
luciferase reporter assay. Conclusion: The MSTRG51053.2
lncRNA may function as a
ceRNA for miR-432-5p to regulate the DDP resistance in NSCLC. The MGST1, MGST3, GST-ω1, and ABCG2 mRNAs, miR-432-5p and miR-665
miRNAs, and MSTRG51053.2 and PPAN lncRNAs can serve as potential DDP drug targets to reverse DDP resistance in NSCLC.