title: Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy.
abstract: Current antiangiogenesis therapy relies on inhibiting newly developed immature tumor blood vessels and starving tumor cells. This strategy has shown transient and modest efficacy. Here, we report a better approach to target cancer-associated endothelial cells (ECs), reverse permeability and leakiness of tumor blood vessels, and improve delivery of chemotherapeutic agents to the tumor. First, we identified deregulated microRNAs (miRs) from patient-derived cancer-associated ECs. Silencing these miRs led to decreased vascular permeability and increased maturation of blood vessels. Next, we screened a thioaptamer (TA) library to identify TAs selective for tumor-associated ECs. An annexin A2-targeted TA was identified and used for delivery of miR106b-5p and miR30c-5p inhibitors, resulting in vascular maturation and antitumor effects without inducing hypoxia. These findings could have implications for improving vascular-targeted therapy.
authors: Department of Gynecologic Oncology and Reproductive Medicine.|Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Lingegowda S
authors: LS
authors: Mangala
authors: Institute of Molecular Medicine.|Department of Nanomedicine and Biomedical Engineering, The University of Texas Health Science Center, Houston, Texas, USA.
authors: Hongyu
authors: H
authors: Wang
authors: Department of Gynecologic Oncology and Reproductive Medicine.|Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Dahai
authors: D
authors: Jiang
authors: Department of Gynecologic Oncology and Reproductive Medicine.
authors: Sherry Y
authors: SY
authors: Wu
authors: Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA.
authors: Anoma
authors: A
authors: Somasunderam
authors: Institute of Molecular Medicine.|Department of Nanomedicine and Biomedical Engineering, The University of Texas Health Science Center, Houston, Texas, USA.
authors: David E
authors: DE
authors: Volk
authors: Institute of Molecular Medicine.
authors: Ganesh L R
authors: GLR
authors: Lokesh
authors: Institute of Molecular Medicine.
authors: Xin
authors: X
authors: Li
authors: Department of Gynecologic Oncology and Reproductive Medicine.
authors: Sunila
authors: S
authors: Pradeep
authors: AM Biotechnologies, Houston, Texas, USA.
authors: Xianbin
authors: X
authors: Yang
authors: Department of Gynecologic Oncology and Reproductive Medicine.
authors: Monika
authors: M
authors: Haemmerle
authors: Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Cristian
authors: C
authors: Rodriguez-Aguayo
authors: Department of Gynecologic Oncology and Reproductive Medicine.
authors: Archana S
authors: AS
authors: Nagaraja
authors: Department of Gynecologic Oncology and Reproductive Medicine.
authors: Rajesha
authors: R
authors: Rupaimoole
authors: Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Emine
authors: E
authors: Bayraktar
authors: Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Recep
authors: R
authors: Bayraktar
authors: Institute of Molecular Medicine.
authors: Li
authors: L
authors: Li
authors: Biomedical Research Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors: Takemi
authors: T
authors: Tanaka
authors: Department of Gynecologic Oncology and Reproductive Medicine.
authors: Wei
authors: W
authors: Hu
authors: Department of Gynecologic Oncology and Reproductive Medicine.
authors: Cristina
authors: C
authors: Ivan
authors: Department of Gynecologic Oncology and Reproductive Medicine.
authors: Kshipra M
authors: KM
authors: Gharpure
authors: Department of Gynecologic Oncology and Reproductive Medicine.
authors: Michael H
authors: MH
authors: McGuire
authors: Institute of Molecular Medicine.|Department of Nanomedicine and Biomedical Engineering, The University of Texas Health Science Center, Houston, Texas, USA.
authors: Varatharasa
authors: V
authors: Thiviyanathan
authors: Department of Gynecologic Oncology and Reproductive Medicine.|Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Xinna
authors: X
authors: Zhang
authors: Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Sourindra N
authors: SN
authors: Maiti
authors: Institute of Molecular Medicine.
authors: Nataliya
authors: N
authors: Bulayeva
authors: Department of Gynecologic Oncology and Reproductive Medicine.
authors: Hyun-Jin
authors: HJ
authors: Choi
authors: Department of Gynecologic Oncology and Reproductive Medicine.
authors: Piotr L
authors: PL
authors: Dorniak
authors: Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Laurence Jn
authors: LJ
authors: Cooper
authors: Companion DX Reference Lab, Houston, Texas, USA.
authors: Kevin P
authors: KP
authors: Rosenblatt
authors: Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Gabriel
authors: G
authors: Lopez-Berestein
authors: Institute of Molecular Medicine.|Department of Nanomedicine and Biomedical Engineering, The University of Texas Health Science Center, Houston, Texas, USA.|AM Biotechnologies, Houston, Texas, USA.
authors: David G
authors: DG
authors: Gorenstein
authors: Department of Gynecologic Oncology and Reproductive Medicine.|Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Anil K
authors: AK
authors: Sood
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D052157:Aptamers, Nucleotide; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D035683:MicroRNAs / Q000008:administration & dosage*; D053758:Nanoparticles; D009369:Neoplasms / Q000098:blood supply / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D035683:MicroRNAs