MicroRNA-106a confers cisplatin resistance in non-small cell lung cancer A549 cells by targeting adenosine triphosphatase-binding cassette A1

Mol Med Rep. 2015 Jan;11(1):625-32. doi: 10.3892/mmr.2014.2688. Epub 2014 Oct 17.

Abstract

MicroRNAs (miRNAs) have been discovered to have pivotal roles in regulating the drug resistance of various types of human cancer, including cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC). Fewer studies have explored the roles of miR-106a in NSCLC-cell resistance to DDP and its precise molecular mechanism has remained elusive. In the present study, whether miR-106a was able to mediate resistance of the lung cancer cell line A549 to DDP was investigated. Reverse transcription quantitative polymerase chain reaction was used to analyze miR-106a mRNA expression levels. miR-106a expression levels were upregulated in the DDP-resistant cell line A549/DDP compared with its parental cell line, A549. miR-106a-transfection induced DDP-resistance in A549 cells, while repression of miR-106a by anti-miR-106a in A549/DDP resulted in enhanced DDP cytotoxicity. Furthermore, it was discovered that the mechanism of miR-106a-induced DDP resistance involved the expression of adenosine triphosphatase-binding cassette, sub-family A, member 1 (ABCA1), as indicated by transfection of cells with short interfering RNA-ABCA1. The results of the present study suggested a novel mechanism underlying DDP-resistance in NSCLC.

MeSH terms

  • ATP Binding Cassette Transporter 1 / genetics*
  • ATP Binding Cassette Transporter 1 / metabolism
  • Antineoplastic Agents / pharmacology
  • Base Sequence
  • Binding Sites
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • MicroRNAs / genetics*
  • Models, Biological
  • RNA Interference*
  • Signal Transduction

Substances

  • ATP Binding Cassette Transporter 1
  • Antineoplastic Agents
  • MIRN106 microRNA, human
  • MicroRNAs
  • Cisplatin