Transcriptome Sequencing Reveals Key Pathways and Genes Associated with Cisplatin Resistance in Lung Adenocarcinoma A549 Cells

Abstract

Acquired resistance to cisplatin-based chemotherapy frequently occurs in patients with non-small cell lung cancer, and the underlying molecular mechanisms are not well understood. The aim of this study was to investigate whether a distinct gene expression pattern is associated with acquired resistance to cisplatin in human lung adenocarcinoma. Whole-transcriptome sequencing was performed to compare the genome-wide gene expression patterns of the human lung adenocarcinoma A549 cisplatin-resistant cell line A549/DDP with those of its progenitor cell line A549. A total of 1214 differentially expressed genes (DEGs) were identified, 656 of which were upregulated and 558 were downregulated. Functional annotation of the DEGs in the Kyoto Encyclopedia of Genes and Genomes database revealed that most of the identified genes were enriched in the PI3K/AKT, mitogen-activated protein kinase, actin cytoskeleton regulation, and focal adhesion pathways in A549/DDP cells. These results support previous studies demonstrating that the pathways regulating cell proliferation and invasion confer resistance to chemotherapy. Furthermore, the results proved that cell adhesion and cytoskeleton regulation is associated with cisplatin resistance in human lung cancer. Our study provides new promising biomarkers for lung cancer prognosis and potential therapeutic targets for lung cancer treatment.

Over-regulation of microRNA-133b inhibits cell proliferation of cisplatin-induced non-small cell lung cancer cells through PI3K/Akt and JAK2/STAT3 signaling pathway by targeting EGFR

“…The inhibition of the AKT1 expression can reverse the resistance of lung adenocarcinoma mDR cells A549/CDDP to cisplatin (15). Further studies have shown that AKT1-induced resistance of lung cancer to cisplatin is mediated by the signal pathway mTOR-P70S6K1 (15). The present study demonstrated anticancer activity and its mechanism of microRNA-133b on cell proliferation of cisplatin-induced non-small cell lung cancer cells.…”

“…For instance, the overexpression of AKT1 leads the resistance of lung cancer cells to cisplatin. The inhibition of the AKT1 expression can reverse the resistance of lung adenocarcinoma mDR cells A549/CDDP to cisplatin (15). Further studies have shown that AKT1-induced resistance of lung cancer to cisplatin is mediated by the signal pathway mTOR-P70S6K1 (15).…”

Genome-wide single-nucleotide resolution of oxaliplatin–DNA adduct repair in drug-sensitive and -resistant colorectal cancer cell lines

“…Inspection of the oxaliplatin repair slot blots such as in Figure 2A suggested uneven levels of initial damage among the cell lines. Oxaliplatin treatment is known to be influenced by factors such as drug influx, efflux, and neutralization (24)(25)(26). We therefore systematically compared the amount of initial damage incurred following treatment of each cell line with 200 uM oxaliplatin for 2 hours.…”

Screening common signaling pathways associated with drug resistance in non‐small cell lung cancer via gene expression profile analysis

“…Dysregulation of MAPK signaling pathway was shown to correlate with the progression of pancreatic ductal adenocarcinoma. The blockade of MAPK signaling using FBP1‐derived small peptide could overcome the gemcitabine‐induced ERK activation and increase the efficacy of anticancer treatment . In our study, upregulated MAPK signaling level was reported with a concomitant overexpression of activating transcription factor 2 (ATF2), an isoform of P38 MAPK family.…”