HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer

Oncogene. 2013 Mar 28;32(13):1616-25. doi: 10.1038/onc.2012.193. Epub 2012 May 21.

Abstract

HOTAIR is a long intervening non-coding RNA (lincRNA) that associates with the Polycomb Repressive Complex 2 (PRC2) and overexpression is correlated with poor survival for breast, colon and liver cancer patients. In this study, we show that HOTAIR expression is increased in pancreatic tumors compared with non-tumor tissue and is associated with more aggressive tumors. Knockdown of HOTAIR (siHOTAIR) by RNA interference shows that HOTAIR has an important role in pancreatic cancer cell invasion, as reported in other cancer cell lines. In contrast, HOTAIR knockdown in Panc1 and L3.6pL pancreatic cancer cells that overexpress this lincRNA decreased cell proliferation, altered cell cycle progression and induced apoptosis, demonstrating an expanded function of HOTAIR in pancreatic cancer cells compared with other cancer cell lines. Results of gene array studies showed that there was minimal overlap between HOTAIR-regulated genes in pancreatic cells and breast cancer cells, and HOTAIR uniquely suppressed several interferon-related genes and gene sets related to cell cycle progression in pancreatic cancer cells and tumors. Analysis of selected genes suppressed by HOTAIR in Panc1 and L3.6pL cells showed by knockdown of EZH2 and chromatin immunoprecipitation assays that HOTAIR-mediated gene repression was both PRC2-dependent and -independent. HOTAIR knockdown in L3.6pL cells inhibited tumor growth in mouse xenograft model, further demonstrating the pro-oncogenic function of HOTAIR in pancreatic cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Biomarkers, Tumor / physiology
  • Carcinoma, Pancreatic Ductal / diagnosis*
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / physiology
  • Gene Knockdown Techniques
  • Humans
  • Mice
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • RNA, Long Noncoding / physiology*
  • RNA, Small Interfering / pharmacology
  • Transplantation, Heterologous

Substances

  • Biomarkers, Tumor
  • HOTAIR long untranslated RNA, human
  • RNA, Long Noncoding
  • RNA, Small Interfering