MicroRNA-30e reduces cell growth and enhances drug sensitivity to gefitinib in lung carcinoma

Oncotarget. 2017 Jan 17;8(3):4572-4581. doi: 10.18632/oncotarget.13944.

Abstract

MicroRNAs (miRNAs) play critical roles in variousbiological processes,including malignancy. Here, we demonstrated that miR-30e levels were markedly reduced in human lung carcinoma specimens in comparisonwith adjacent normal tissues.In addition, miR-30eamounts were starkly lower in the resistant PC9/gefitinib (PC9G) cancer cells compared with PC9 cells. Meanwhile, miR-30eoverexpression inPC9G cells resulted in reduced cell proliferation and migration,reversing drug resistance to gefitinib.Conversely,miR-30e silencing in PC9 cells increased proliferation as well as migration, and conferred resistance to gefitinib.Moreover, HOXA1, which was identified asa new miR-30etarget, plays important roles in regulating cell fate, early developmental patterns and organogenesis.Importantly, miR-30ealso inhibited PC9G growth in vivo. Taken together, these findings demonstrated that miR-30eshould be considered a tumor suppressor miRNA, which could be used in treatinghuman lung cancer.

Keywords: HOXA1; chemosensitivity; gefitinib; lung cancer; miRNA-30e.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Down-Regulation
  • Drug Resistance, Neoplasm*
  • Gefitinib
  • Gene Expression Regulation, Neoplastic / drug effects
  • Homeodomain Proteins / genetics*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Transplantation
  • Quinazolines / administration & dosage*
  • Quinazolines / pharmacology
  • Transcription Factors / genetics*

Substances

  • Antineoplastic Agents
  • Homeodomain Proteins
  • MIRN30b microRNA, human
  • MicroRNAs
  • Quinazolines
  • Transcription Factors
  • homeobox A1 protein
  • Gefitinib