TY - JOUR
T1 - Long Noncoding RNA Ceruloplasmin Promotes Cancer Growth by Altering Glycolysis
AU - Rupaimoole, Rajesha
AU - Lee, Jaehyuk
AU - Haemmerle, Monika
AU - Ling, Hui
AU - Previs, Rebecca A.
AU - Pradeep, Sunila
AU - Wu, Sherry Y.
AU - Ivan, Cristina
AU - Ferracin, Manuela
AU - Dennison, Jennifer B.
AU - Millward, Niki M.Zacharias
AU - Nagaraja, Archana S.
AU - Gharpure, Kshipra M.
AU - McGuire, Michael
AU - Sam, Nidhin
AU - Armaiz-Pena, Guillermo N.
AU - Sadaoui, Nouara C.
AU - Rodriguez-Aguayo, Cristian
AU - Calin, George A.
AU - Drapkin, Ronny I.
AU - Kovacs, Jeffery
AU - Mills, Gordon B.
AU - Zhang, Wei
AU - Lopez-Berestein, Gabriel
AU - Bhattacharya, Pratip K.
AU - Sood, Anil K.
N1 - Funding Information:
We thank the following for funding support. Portions of this work were supported by the NIH (P30 CA016672, CA109298, UH3TR000943, P50 CA083639, P50 CA098258, U54 CA151668, and U24CA143835), the CPRIT (RP110595), the Ovarian Cancer Research Fund, the United States DOD (OC073399, W81XWH-10-1-0158, and BC085265), the Marcus Foundation, the Red and Charline McCombs Institute for the Early Detection and Treatment of Cancer, the RGK Foundation, the Gilder Foundation, the Blanton-Davis Ovarian Cancer Research Program, and the Betty Anne Asche Murray Distinguished Professorship (to A.K.S.). R.R. is supported in part by the Russell and Diana Hawkins Family Foundation Discovery Fellowship. S.Y.W. is supported by the Ovarian Cancer Research Fund, Foundation for Women’s Cancer, and Cancer Prevention and Research Institute of Texas training grants (RP101502 and RP101489). M.H. is supported by the Deutsche Forschungsgemeinschaft (DFG).
Publisher Copyright:
© 2015 The Authors.
PY - 2015/12/22
Y1 - 2015/12/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84952873436&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84952873436&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2015.11.047
DO - 10.1016/j.celrep.2015.11.047
M3 - Article
C2 - 26686630
AN - SCOPUS:84952873436
SN - 2211-1247
VL - 13
SP - 2395
EP - 2402
JO - Cell Reports
JF - Cell Reports
IS - 11
ER -