miR-199a-5p is involved in doxorubicin resistance of non-small cell lung cancer (NSCLC) cells

Eur J Pharmacol. 2020 Jul 5:878:173105. doi: 10.1016/j.ejphar.2020.173105. Epub 2020 Apr 9.

Abstract

Non-small cell lung cancer (NSCLC) is one of the prevalent and deadly cancers worldwide. Chemotherapy resistance is one of the most challenging problems for NSCLC and other cancer treatment. Recent study suggested that miRNAs are involved in therapeutic functions of chemotherapy during cancer treatment. Our present study established doxorubicin (Dox) resistant NSCLC A549 and H460 cells (named A549Dox/R and H460 Dox/R). We found that miR-199a-5p was significantly down regulated in Dox resistant cells. Over expression of miR-199a-5p can increase the Dox sensitivity of resistant cells. Among various targets of miR-199a-5p, chemoresistance can increase the expression of ABCC1 and HIF-1α. Gain and loss of function studies confirmed that both ABCC1 and HIF-1α were involved in the chemoresistance of NSCLC cells. Collectively, our data showed that miR-199a-5p regulated expression of ABCC1 and HIF-1α were involved in Dox resistance of NSCLC.

Keywords: ABCC1; Dox; HIF-1α; NSCLC; miR-199a-5p.

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Doxorubicin / pharmacology*
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Lung Neoplasms / drug therapy*
  • MicroRNAs / metabolism*
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism

Substances

  • Antibiotics, Antineoplastic
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MicroRNAs
  • Multidrug Resistance-Associated Proteins
  • mirn199 microRNA, human
  • Doxorubicin
  • multidrug resistance-associated protein 1