Identifying and targeting angiogenesis-related microRNAs in ovarian cancer

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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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Correspondence to Lingegowda S. Mangala or 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) doi:10.1038/s41388-019-0862-y

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