title: A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer.
abstract: A deeper mechanistic understanding of tumour angiogenesis regulation is needed to improve current anti-angiogenic therapies. Here we present evidence from systems-based miRNA analyses of large-scale patient data sets along with in vitro and in vivo experiments that miR-192 is a key regulator of angiogenesis. The potent anti-angiogenic effect of miR-192 stems from its ability to globally downregulate angiogenic pathways in cancer cells through regulation of EGR1 and HOXB9. Low miR-192 expression in human tumours is predictive of poor clinical outcome in several cancer types. Using 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) nanoliposomes, we show that miR-192 delivery leads to inhibition of tumour angiogenesis in multiple ovarian and renal tumour models, resulting in tumour regression and growth inhibition. This anti-angiogenic and anti-tumour effect is more robust than that observed with an anti-VEGF antibody. Collectively, these data identify miR-192 as a central node in tumour angiogenesis and support the use of miR-192 in an anti-angiogenesis therapy.
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Sherry Y
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Rajesha
authors.initials: R
authors.lastname: Rupaimoole
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.|Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province 215006, China.
authors.forename: Fangrong
authors.initials: F
authors.lastname: Shen
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Sunila
authors.initials: S
authors.lastname: Pradeep
authors.affiliation: Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.|Department of Medicine, The University of North Carolina, Chapel Hill, North Carolina 27599 USA.
authors.forename: Chad V
authors.initials: CV
authors.lastname: Pecot
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.|Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Cristina
authors.identifier: http://orcid.org/0000-0002-4848-0168
authors.initials: C
authors.lastname: Ivan
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Archana S
authors.initials: AS
authors.lastname: Nagaraja
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Kshipra M
authors.initials: KM
authors.lastname: Gharpure
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.|Biological Sciences Platform, Sunnybrook Research Institute, Toronto, Ontario, Canada, M4N 3M5.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pham
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Hatakeyama
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: McGuire
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Monika
authors.initials: M
authors.lastname: Haemmerle
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Viviana
authors.initials: V
authors.lastname: Vidal-Anaya
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Courtney
authors.identifier: http://orcid.org/0000-0003-2685-0217
authors.initials: C
authors.lastname: Olsen
authors.affiliation: Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.|Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Cristian
authors.identifier: http://orcid.org/0000-0002-7880-7723
authors.initials: C
authors.lastname: Rodriguez-Aguayo
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Justyna
authors.initials: J
authors.lastname: Filant
authors.affiliation: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Ehsan A
authors.initials: EA
authors.lastname: Ehsanipour
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.|Department of Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Shelley M
authors.initials: SM
authors.lastname: Herbrich
authors.affiliation: Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Sourindra N
authors.initials: SN
authors.lastname: Maiti
authors.affiliation: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Ji Hoon
authors.identifier: http://orcid.org/0000-0003-3924-0434
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Xinna
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.|Department of Immunology Laboratory, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors.forename: Hee-Dong
authors.initials: HD
authors.lastname: Han
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Guillermo N
authors.initials: GN
authors.lastname: Armaiz-Pena
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Elena G
authors.initials: EG
authors.lastname: Seviour
authors.affiliation: Department of Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Sue
authors.initials: S
authors.lastname: Tucker
authors.affiliation: Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Da
authors.initials: D
authors.lastname: Yang
authors.affiliation: Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Laurence J N
authors.identifier: http://orcid.org/0000-0003-1460-3905
authors.initials: LJ
authors.lastname: Cooper
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Karmanos Cancer Institute, Detroit, Michigan 48201, USA.
authors.forename: Rouba
authors.initials: R
authors.lastname: Ali-Fehmi
authors.affiliation: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Menashe
authors.initials: M
authors.lastname: Bar-Eli
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Prahlad T
authors.initials: PT
authors.lastname: Ram
authors.affiliation: Department of Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Baggerly
authors.affiliation: Department of Medicine, The University of North Carolina, Chapel Hill, North Carolina 27599 USA.|Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lopez-Berestein
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.|Center for Molecular Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.|Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.|Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D053263:Gene Regulatory Networks; D015316:Genetic Therapy; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000628:therapy; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000628:therapy; D010713:Phosphatidylcholines; D047368:Tumor Burden
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C491257:HOXB9 protein, human; D018398:Homeodomain Proteins; C546783:MIRN192 microRNA, human; D035683:MicroRNAs; D010713:Phosphatidylcholines; C017251:1,2-oleoylphosphatidylcholine