Research Papers:

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

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

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Oncotarget. 2015; 6:10840-10852. https://doi.org/10.18632/oncotarget.3450

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Yating Cheng1, Indira Jutooru1,4, Gayathri Chadalapaka1, J. Christopher Corton3, Stephen Safe1,2

1Department of Veterinary Physiology and Pharmacology, Texas A&M University, 4466 TAMU, College Station, TX 77843-4466, USA

2Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030–3303, USA

3Integrated Systems Toxicology Division, US-EPA, MD B143-06, Research Triangle Park, NC 27711, USA

4Covance, Inc., Madison, WI 53704, USA

Correspondence to:

Stephen Safe, e-mail: [email protected]

Keywords: HOTTIP, lncRNA, HOX genes, pro-oncogenic, HOTAIR

Received: December 15, 2014     Accepted: February 24, 2015     Published: March 25, 2015


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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