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.