title: 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.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Rajesha
authors.initials: R
authors.lastname: Rupaimoole
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jaehyuk
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Monika
authors.initials: M
authors.lastname: Haemmerle
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Ling
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Previs
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Sunila
authors.initials: S
authors.lastname: Pradeep
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Sherry Y
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ivan
authors.affiliation: Department of Experimental and Diagnostic Medicine and Interdepartment Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferracin
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Dennison
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Niki M Zacharias
authors.initials: NMZ
authors.lastname: Millward
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Archana S
authors.initials: AS
authors.lastname: Nagaraja
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Kshipra M
authors.initials: KM
authors.lastname: Gharpure
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: McGuire
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Nidhin
authors.initials: N
authors.lastname: Sam
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Guillermo N
authors.initials: GN
authors.lastname: Armaiz-Pena
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Nouara C
authors.initials: NC
authors.lastname: Sadaoui
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Cristian
authors.initials: C
authors.lastname: Rodriguez-Aguayo
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.affiliation: Obstetrics, Gynecology and Pathology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ronny I
authors.initials: RI
authors.lastname: Drapkin
authors.affiliation: Institute of Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jeffery
authors.initials: J
authors.lastname: Kovacs
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lopez-Berestein
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Pratip K
authors.initials: PK
authors.lastname: Bhattacharya
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: asood@mdanderson.org.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002570:Ceruloplasmin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D034622:RNA Interference; D012319:RNA Polymerase II / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor; D002570:Ceruloplasmin; D012319:RNA Polymerase II; D005956:Glucose-6-Phosphate Isomerase