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The long non-coding RNA HOTTIP enhances pancreatic cancer cell proliferation,
survival and migration
#MMPMID25912306
Cheng Y
; Jutooru I
; Chadalapaka G
; Corton JC
; Safe S
Oncotarget
2015[May]; 6
(13
): 10840-52
PMID25912306
show ga
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.
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