Identifying and targeting angiogenesis-related microRNAs in ovarian cancer

Oncogene. 2019 Aug;38(33):6095-6108. doi: 10.1038/s41388-019-0862-y. Epub 2019 Jul 9.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Carcinoma, Ovarian Epithelial / blood supply
  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Carcinoma, Ovarian Epithelial / genetics*
  • Carcinoma, Ovarian Epithelial / pathology
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs* / antagonists & inhibitors
  • MicroRNAs* / genetics
  • Molecular Targeted Therapy / methods
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / genetics*
  • Ovarian Neoplasms / blood supply
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • RNA, Small Interfering / pharmacology
  • RNA, Small Interfering / therapeutic use
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • MIRN204 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering