Profiles and Bioinformatics Analysis of Differentially Expressed Circrnas in Taxol-Resistant Non-Small Cell Lung Cancer Cells

Cell Physiol Biochem. 2018;48(5):2046-2060. doi: 10.1159/000492543. Epub 2018 Aug 10.

Abstract

Background/aims: Circular RNAs (circRNAs) act as microRNA (miRNA) sponges that regulate gene expression and are involved in physiological and pathological processes. In this study, we evaluated the roles of circRNAs in the chemoresistance of non-small cell lung cancer (NSCLC) to taxol.

Methods: High-throughput circRNA microarrays were employed to investigate the circRNA profiles of parental A549 and taxol-resistant A549/Taxol cells. We predicted the miRNA targets of differentially expressed circRNAs via miRNA prediction software and then constructed a circRNA/miRNA network using Cytoscape. Bioinformatics analyses were performed to annotate dysregulated circRNAs in detail.

Results: We detected 2909 significantly upregulated and 8372 downregulated circRNAs in A549/Taxol cells compared with A549 cells. The circRNA/miRNA network displayed their interactions, suggesting that circRNAs exert biological effects by absorbing and sequestering miRNA molecules. Computational Gene Ontology and pathway analyses were used to determine the biological function and signaling pathways of host genes of dysregulated circRNAs and to identify potential molecular mechanisms prompting the resistance of NSCLC to taxol.

Conclusion: This study focusing on circRNAs related to taxol resistance provides a basis for clarifying the development and progression of drug resistance and for identifying therapeutic targets in NSCLC.

Keywords: Bioinformatics analysis; Circrna; Microarray; NSCLC; Taxol resistance.

MeSH terms

  • A549 Cells
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Computational Biology
  • Down-Regulation / drug effects
  • Drug Resistance, Neoplasm / genetics*
  • Gene Regulatory Networks
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • MicroRNAs / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Paclitaxel / pharmacology*
  • Paclitaxel / therapeutic use
  • RNA / metabolism*
  • RNA, Circular
  • Transcriptome / drug effects*
  • Up-Regulation / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • MicroRNAs
  • RNA, Circular
  • RNA
  • Paclitaxel