Long Noncoding RNA Ceruloplasmin Promotes Cancer Growth by Altering Glycolysis.

Abstract

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.

• Authors: Rajesha Rupaimoole, Jaehyuk Lee, Monika Haemmerle, Hui Ling, Rebecca A Previs, Sunila Pradeep, Sherry Y Wu, Cristina Ivan, Manuela Ferracin, Jennifer B Dennison, Niki M Zacharias Millward, Archana S Nagaraja, Kshipra M Gharpure, Michael McGuire, Nidhin Sam, Guillermo N Armaiz-Pena, Nouara C Sadaoui, Cristian Rodriguez-Aguayo, George A Calin, Ronny I Drapkin, Jeffery Kovacs, Gordon B Mills, Wei Zhang, Gabriel Lopez-Berestein, Pratip K Bhattacharya, Anil K Sood
• Journal: Cell reports (Cell Rep) Vol. 13 Issue 11 Pg. 2395-2402 (Dec 22 2015) ISSN: 2211-1247 [Electronic] United States
• PMID: 26686630 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• RNA, Long Noncoding
• RNA, Small Interfering
• STAT1 Transcription Factor
• Ceruloplasmin
• RNA Polymerase II
• Glucose-6-Phosphate Isomerase

Topics

• Animals
• Apoptosis
• Cell Line, Tumor
• Cell Proliferation
• Ceruloplasmin (antagonists & inhibitors, genetics, metabolism)
• Disease Progression
• Female
• Glucose-6-Phosphate Isomerase (genetics, metabolism)
• Glycolysis
• Humans
• Kaplan-Meier Estimate
• Mice
• Mice, Nude
• Ovarian Neoplasms (metabolism, mortality, pathology)
• RNA Interference
• RNA Polymerase II (metabolism)
• RNA, Long Noncoding (antagonists & inhibitors, metabolism)
• RNA, Small Interfering (metabolism)
• STAT1 Transcription Factor (metabolism)
• Transplantation, Heterologous