Long Noncoding RNA Ceruloplasmin Promotes Cancer Growth by Altering Glycolysis. Cell Rep 2015 Dec 22;13(11):2395-2402
Date
12/22/2015Pubmed ID
26686630Pubmed Central ID
PMC4691557DOI
10.1016/j.celrep.2015.11.047Scopus ID
2-s2.0-84952873436 (requires institutional sign-in at Scopus site) 95 CitationsAbstract
Long noncoding RNAs (lncRNAs) significantly influence the development and regulation of genome expression in cells. Here, we demonstrate the role of lncRNA ceruloplasmin (NRCP) in cancer metabolism and elucidate functional effects leading to increased tumor progression. NRCP was highly upregulated in ovarian tumors, and knockdown of NRCP resulted in significantly increased apoptosis, decreased cell proliferation, and decreased glycolysis compared with control cancer cells. In an orthotopic mouse model of ovarian cancer, siNRCP delivered via a liposomal carrier significantly reduced tumor growth compared with control treatment. We identified NRCP as an intermediate binding partner between STAT1 and RNA polymerase II, leading to increased expression of downstream target genes such as glucose-6-phosphate isomerase. Collectively, we report a previously unrecognized role of the lncRNA NRCP in modulating cancer metabolism. As demonstrated, DOPC nanoparticle-incorporated siRNA-mediated silencing of this lncRNA in vivo provides therapeutic avenue toward modulating lncRNAs in cancer.
Author List
Rupaimoole R, Lee J, Haemmerle M, Ling H, Previs RA, Pradeep S, Wu SY, Ivan C, Ferracin M, Dennison JB, Millward NMZ, Nagaraja AS, Gharpure KM, McGuire M, Sam N, Armaiz-Pena GN, Sadaoui NC, Rodriguez-Aguayo C, Calin GA, Drapkin RI, Kovacs J, Mills GB, Zhang W, Lopez-Berestein G, Bhattacharya PK, Sood AKAuthor
Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Cell Line, Tumor
Cell Proliferation
Ceruloplasmin
Disease Progression
Female
Glucose-6-Phosphate Isomerase
Glycolysis
Humans
Kaplan-Meier Estimate
Mice
Mice, Nude
Ovarian Neoplasms
RNA Interference
RNA Polymerase II
RNA, Long Noncoding
RNA, Small Interfering
STAT1 Transcription Factor
Transplantation, Heterologous