Long noncoding RNA CCAT1 acts as an oncogene and promotes chemoresistance in docetaxel-resistant lung adenocarcinoma cells

Oncotarget. 2016 Sep 20;7(38):62474-62489. doi: 10.18632/oncotarget.11518.

Abstract

Chemoresistance remains one of the major obstacles in clinical treatment of lung adenocarcinoma (LAD). Indeed, docetaxel-resistant LAD cells present chemoresistance and epithelial-to-mesenchymal transition phenotypes. Long non-coding RNAs (lncRNAs) are known to promote tumorigenesis in many cancer types. Here, we showed that the lncRNA colon cancer-associated transcript-1 (CCAT1) was upregulated in docetaxel-resistant LAD cells. Furthermore, downregulation of CCAT1 decreased chemoresistance, inhibited proliferation, enhanced apoptosis and reversed the epithelial-to-mesenchymal transition phenotype of docetaxel-resistant LAD cells. We also found that the oncogenic function of CCAT1 in docetaxel-resistant LAD cells depended on the sponging of let-7c. In turn, the sponging of let-7c by CCAT1 released Bcl-xl (a let-7c target), thereby promoting the acquisition of chemoresistance and epithelial-to-mesenchymal transition phenotypes in docetaxel-resistant LAD cells. Our data reveal a novel pathway underlying chemoresistance and the epithelial-to-mesenchymal transition in docetaxel-resistant LAD cells.

Keywords: chemoresistance; epithelial-to-mesenchymal transition; let-7c; lncRNA CCAT1; lung adenocarcinoma (LAD).

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics*
  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Docetaxel
  • Drug Resistance, Neoplasm*
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Oncogenes
  • Phenotype
  • RNA, Long Noncoding / genetics*
  • Taxoids / pharmacology*
  • bcl-X Protein / metabolism

Substances

  • BCL2L1 protein, human
  • CCAT1 long noncoding RNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Taxoids
  • bcl-X Protein
  • mirnlet7 microRNA, human
  • Docetaxel