LincRNA-ROR promotes invasion, metastasis and tumor growth in pancreatic cancer through activating ZEB1 pathway

Cancer Lett. 2016 May 1;374(2):261-71. doi: 10.1016/j.canlet.2016.02.018. Epub 2016 Feb 16.

Abstract

Pancreatic cancer (PC) remains one of the most lethal malignant tumors; early distant metastasis commonly results in poor prognosis. Recent studies confirmed the pivotal role of the long non-coding RNAs (lncRNAs) in tumorigenesis and metastasis of malignant tumors, including PC. However, little is known about the role of LincRNA-ROR (linc-ROR) in PC. In the present study, we found that linc-ROR was upregulated in PC tissues. Overexpression of linc-ROR promoted cells proliferation, migration, invasion and metastasis both in vitro and in a mouse model. Contrarily, knockdown of linc-ROR attenuated proliferation, invasion and distant metastasis. Mechanistically, we confirmed that linc-ROR up-regulates ZEB1 and then induces epithelial-mesenchymal transition (EMT), which promotes the aggressive biological behaviors of PC. Together, these results indicate that linc-ROR acts as an important regulator of ZEB1, can promote invasion and metastasis in PC, and may represent a novel therapeutic target.

Keywords: Epithelial-mesenchymal transition; LincRNA-ROR; Metastasis; Pancreatic cancer; ZEB1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Gene Knockdown Techniques
  • Heterografts
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Up-Regulation
  • Zinc Finger E-box-Binding Homeobox 1

Substances

  • Homeodomain Proteins
  • Linc-RNA-RoR, human
  • RNA, Long Noncoding
  • Transcription Factors
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1