The long non-coding RNA HOTTIP enhances pancreatic cancer cell proliferation, survival and migration

Yating Cheng, Indira Jutooru, Gayathri Chadalapaka, J. Christopher Corton, Stephen Safe

Research output: Contribution to journalArticle

117 Scopus citations

Abstract

HOTTIP is a long non-coding RNA (lncRNA) transcribed from the 5′ tip of the HOXA locus and is associated with the polycomb repressor complex 2 (PRC2) and WD repeat containing protein 5 (WDR5)/mixed lineage leukemia 1 (MLL1) chromatin modifying complexes. HOTTIP is expressed in pancreatic cancer cell lines and knockdown of HOTTIP by RNA interference (siHOTTIP) in Panc1 pancreatic cancer cells decreased proliferation, induced apoptosis and decreased migration. In Panc1 cells transfected with siHOTTIP, there was a decrease in expression of 757 genes and increased expression of 514 genes, and a limited gene analysis indicated that HOTTIP regulation of genes is complex. For example, Aurora kinase A, an important regulator of cell growth, is coregulated by MLL and not WDR5 and, in contrast to previous studies in liver cancer cells, HOTTIP does not regulate HOXA13 but plays a role in regulation of several other HOX genes including HOXA10, HOXB2, HOXA11, HOXA9 and HOXA1. Although HOTTIP and the HOX-associated lncRNA HOTAIR have similar pro-oncogenic functions, they regulate strikingly different sets of genes in Panc1 cells and in pancreatic tumors.

Original languageEnglish (US)
Pages (from-to)10840-10852
Number of pages13
JournalOncotarget
Volume6
Issue number13
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • HOTAIR
  • HOTTIP
  • HOX genes
  • LncRNA
  • Pro-oncogenic

ASJC Scopus subject areas

  • Oncology

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