The long non-coding RNA HOTTIP enhances pancreatic cancer cell proliferation, survival and migration.
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.
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA.
Yating
Y
Cheng
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA.|Covance, Inc., Madison, WI 53704, USA.
Indira
I
Jutooru
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA.
Gayathri
G
Chadalapaka
Integrated Systems Toxicology Division, Research Triangle Park, NC 27711, USA.
J Christopher
JC
Corton
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA.|Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
Stephen
S
Safe
D000818:Animals; D017209:Apoptosis; D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008819:Mice, Nude; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D000067492:RNAi Therapeutics; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D018398:Homeodomain Proteins; C497422:KMT2A protein, human; D062085:RNA, Long Noncoding; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C576917:AURKA protein, human; D064096:Aurora Kinase A
HOTAIR; HOTTIP; HOX genes; lncRNA; pro-oncogenic