LncRNA HOTAIR acts a competing endogenous RNA to control the expression of notch3 via sponging miR-613 in pancreatic cancer

Oncotarget. 2017 May 16;8(20):32905-32917. doi: 10.18632/oncotarget.16462.


Pancreatic cancer is one of the most deadly cancers with a poor prognosis. Though studies have implicated the roles of microRNAs in pancreatic cancer progression, little is known about the role of miR-613 in pancreatic cancer. In the present study, the expression of miR-613 was down-regulated in pancreatic cancer tissues and cancer cell lines. Down-regulation of miR-613 was positively correlated with tumor differentiation, advanced TNM stage, nodal metastasis and shorter overall survival in patients with pancreatic cancer. Overexpression of miR-613 suppressed cell proliferation, invasion and migration, and induced cell apoptosis and cell cycle arrest at G0/G1 phase in pancreatic cancer cells. Bioinformatics analysis, luciferase reporter assay and rescue experiments showed that notch3 was a direct target of miR-613. MiR-613 was inversely correlated with notch3 expression in pancreatic cancer tissues. The long non-coding RNA, HOX transcript antisense RNA (HOTAIR) was up-regulated in both pancreatic cancer tissues and cancer cell lines, and HOTAIR suppressed the expression of miR-613 via functioning as a competing endogenous RNA. In vivo studies showed that stable overexpression of miR-613 or knock-down of HOTAIR suppressed tumor growth and also reduced the expression of notch3. In conclusion, these results suggest that HOTAIR functions as a competing endogenous RNA to regulate notch3 expression via sponging miR-613 in pancreatic cancer.

Keywords: HOTAIR; cell proliferation; invasion and migration; miR-613; pancreatic cancer.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Line, Tumor
  • Down-Regulation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Staging
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology*
  • RNA, Long Noncoding / genetics*
  • Receptor, Notch3 / genetics*
  • Survival Analysis
  • Up-Regulation


  • 3' Untranslated Regions
  • HOTAIR long untranslated RNA, human
  • MIRN613 microRNA, human
  • MicroRNAs
  • NOTCH3 protein, human
  • RNA, Long Noncoding
  • Receptor, Notch3