Identifying and targeting angiogenesis-related microRNAs in ovarian cancer

识别和靶向卵巢癌中的血管生成相关微小RNA

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作者:Xiuhui Chen, Lingegowda S Mangala, Linda Mooberry, Emine Bayraktar, Santosh K Dasari, Shaolin Ma, Cristina Ivan, Karem A Court, Cristian Rodriguez-Aguayo, Recep Bayraktar, Sangram Raut, Nirupama Sabnis, Xianchao Kong, Xianbin Yang, Gabriel Lopez-Berestein, Andras G Lacko, Anil K Sood

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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