Cell Reports (Dec 2015)
Long Noncoding RNA Ceruloplasmin Promotes Cancer Growth by Altering Glycolysis
- 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
Affiliations
- Rajesha Rupaimoole
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Jaehyuk Lee
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Monika Haemmerle
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Hui Ling
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Rebecca A. Previs
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Sunila Pradeep
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Sherry Y. Wu
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Cristina Ivan
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Manuela Ferracin
- Department of Experimental and Diagnostic Medicine and Interdepartment Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy
- Jennifer B. Dennison
- Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Niki M. Zacharias Millward
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Archana S. Nagaraja
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Kshipra M. Gharpure
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Michael McGuire
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Nidhin Sam
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Guillermo N. Armaiz-Pena
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Nouara C. Sadaoui
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Cristian Rodriguez-Aguayo
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- George A. Calin
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Ronny I. Drapkin
- Obstetrics, Gynecology and Pathology, University of Pennsylvania, Philadelphia, PA 19104, USA
- Jeffery Kovacs
- Institute of Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Gordon B. Mills
- Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Wei Zhang
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Gabriel Lopez-Berestein
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Pratip K. Bhattacharya
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Anil K. Sood
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- DOI
- https://doi.org/10.1016/j.celrep.2015.11.047
- Journal volume & issue
-
Vol. 13,
no. 11
pp. 2395 – 2402
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.
