Negative Regulation of PTEN by MicroRNA-221 and Its Association with Drug Resistance and Cellular Senescence in Lung Cancer Cells

Biomed Res Int. 2018 Jan 30:2018:7908950. doi: 10.1155/2018/7908950. eCollection 2018.

Abstract

Objective: Chemotherapy is the routine method for treating many cancers, but long-term treatment may result in developing resistance to the drugs. The aim of this study was to identify whether noncoding RNAs play a role in drug resistance and how they affect drug resistance.

Materials and methods: The expression levels of miR-221 in different lung cancer cell lines H226, H1299, and A549 were measured. H1299 and A549 cell lines were transfected to overexpress and downexpress miR-221, and cell viability and cell senescence were determined. The PTEN/Akt pathway was then examined by real-time polymerase chain reaction and Western blot analysis.

Results: MiR-221 together with proteins MDR1 and ABCG2 was upregulated in Cisplatin-resistant A549 lung cancer cells. Anti-miR-221 inhibits proliferation and induces senescence in lung cancer cells. PTEN/Akt pathway axis was identified as a target of drug resistance induced by miR-221.

Conclusion: Our results revealed that miR-221 is an important regulator for chemotherapy sensitivity and showed miR-221 as a potential target for drug sensitization.

MeSH terms

  • A549 Cells
  • Cell Proliferation
  • Cellular Senescence*
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • PTEN Phosphohydrolase / antagonists & inhibitors*
  • PTEN Phosphohydrolase / genetics
  • RNA, Neoplasm / biosynthesis*
  • RNA, Neoplasm / genetics

Substances

  • MIRN221 microRNA, human
  • MicroRNAs
  • RNA, Neoplasm
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Cisplatin