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Identifying and targeting angiogenesis-related microRNAs in ovarian cancer

Oncogene volume 38, pages 6095–6108 (2019)Cite this article

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Abstract

Current anti-angiogenic therapy for cancer is based mainly on inhibition of the vascular endothelial growth factor pathway. However, due to the transient and only modest benefit from such therapy, additional approaches are needed. Deregulation of microRNAs (miRNAs) has been demonstrated to be involved in tumor angiogenesis and offers opportunities for a new therapeutic approach. However, effective miRNA-delivery systems are needed for such approaches to be successful. In this study, miRNA profiling of patient data sets, along with in vitro and in vivo experiments, revealed that miR-204-5p could promote angiogenesis in ovarian tumors through THBS1. By binding with scavenger receptor class B type 1 (SCARB1), reconstituted high-density lipoprotein–nanoparticles (rHDL–NPs) were effective in delivering miR-204-5p inhibitor (miR-204-5p-inh) to tumor sites to suppress tumor growth. These results offer a new understanding of miR-204-5p in regulating tumor angiogenesis.

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Acknowledgements

This work is supported, in part, by the National Institutes of Health (CA016672, UH3TR000943, P50 CA217685, P50 CA098258, R35 CA209904), Ovarian Cancer Research Fund, Inc. (Program Project Development Grant), Mr. and Mrs. Daniel P. Gordon, The Blanton-Davis Ovarian Cancer Research Program, the American Cancer Society Research Professor Award, and the Frank McGraw Memorial Chair in Cancer Research (AKS) and CPRIT (DP150091; LSM). SKD was supported by Foundation for Women’s Cancer Grant, CRA was supported by the P50 CA217685 from the SPORE in Ovarian Cancer at MD Anderson.

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  1. These authors contributed equally: Xiuhui Chen, Lingegowda S. Mangala

Authors and Affiliations

  1. Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Xiuhui Chen, Lingegowda S. Mangala, Emine Bayraktar, Santosh K. Dasari, Shaolin Ma, Karem A. Court & Anil K. Sood

  2. Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China

    Xiuhui Chen & Xianchao Kong

  3. Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Lingegowda S. Mangala, Emine Bayraktar, Cristina Ivan, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein & Anil K. Sood

  4. Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX, USA

    Linda Mooberry, Sangram Raut, Nirupama Sabnis & Andras G. Lacko

  5. Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Cristina Ivan, Cristian Rodriguez-Aguayo, Recep Bayraktar & Gabriel Lopez-Berestein

  6. AM Biotechnologies, Houston, TX, USA

    Xianbin Yang

  7. Department of Pediatrics, University of North Texas Health Science Center, Fort Worth, TX, USA

    Andras G. Lacko

  8. Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Anil K. Sood

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Chen, X., Mangala, L.S., Mooberry, L. et al. Identifying and targeting angiogenesis-related microRNAs in ovarian cancer. Oncogene 38, 6095–6108 (2019). https://doi.org/10.1038/s41388-019-0862-y

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