LncRNA-DANCR contributes to lung adenocarcinoma progression by sponging miR-496 to modulate mTOR expression

J Cell Mol Med. 2018 Mar;22(3):1527-1537. doi: 10.1111/jcmm.13420. Epub 2017 Dec 20.


Long non-coding RNAs (lncRNAs) have emerged as new and important regulators of pathological processes including tumour development. In this study, we demonstrated that differentiation antagonizing non-protein coding RNA (DANCR) was up-regulated in lung adenocarcinoma (ADC) and that the knockdown of DANCR inhibited tumour cell proliferation, migration and invasion and restored cell apoptosis rescued; cotransfection with a miR-496 inhibitor reversed these effects. Luciferase reporter assays showed that miR-496 directly modulated DANCR; additionally, we used RNA-binding protein immunoprecipitation (RIP) and RNA pull-down assays to further confirm that the suppression of DANCR by miR-496 was RISC-dependent. Our study also indicated that mTOR was a target of miR-496 and that DANCR could modulate the expression levels of mTOR by working as a competing endogenous RNA (ceRNA). Furthermore, the knockdown of DANCR reduced tumour volumes in vivo compared with those of the control group. In conclusion, this study showed that DANCR might be an oncogenic lncRNA that regulates mTOR expression through directly binding to miR-496. DANCR may be regarded as a biomarker or therapeutic target for ADC.

Keywords: DANCR; mTOR; ceRNA; lung adenocarcinoma; miR-496; sponge.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / metabolism
  • Adenocarcinoma of Lung / pathology
  • Animals
  • Antagomirs / genetics
  • Antagomirs / metabolism
  • Apoptosis / genetics
  • Base Sequence
  • Binding Sites
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Gene Expression Regulation, Neoplastic*
  • HEK293 Cells
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA-Induced Silencing Complex / genetics
  • RNA-Induced Silencing Complex / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics*
  • TOR Serine-Threonine Kinases / metabolism
  • Tumor Burden
  • Xenograft Model Antitumor Assays


  • Antagomirs
  • DANCR long noncoding RNA, human
  • MIRN496 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA-Induced Silencing Complex
  • MTOR protein, human
  • TOR Serine-Threonine Kinases