Project description:The 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. To identify potential molecular mechanisms by which miR-204-5p exerts its pro-angiogenic effects, we performed a gene expression microarray of HeyA8-MDR cells following treatment with miR-204-5p-inh.
Project description: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.
Project description:Ovulation is induced by the luteinizing hormone surge and accompanied by granulosa cell luteinization and ovarian angiogenesis. Sema3E-Plexin-D1 pathway regulates angiogenesis in other tissues, but its role in the ovary was unknown. We report herein that the expression of Sema3E and its receptor, Plexin-D1, is dynamically regulated in the mouse ovary downstream of the LH surge. This regulation is mediated by CCAAT/enhancer-binding proteins α and β through modulating chromatin accessibility. Intraovarian injection of recombinant Sema3E results in reduced ovulation, impaired corpus luteum formation, and aberrant ovarian angiogenesis. These in vivo physiological abnormalities are consistent with altered expression of genes regulating these processes, and with data from in vitro cultured granulosa cells and/or ovarian stromal tissues treated with Sema3E or Plexin-D1 neutralizing antibody. Our findings shed light on the important role of Sema3E-Plexin-D1 pathway in the ovary, pinpointing it as a potential therapeutic target for fertility and infertility management.
Project description:Angiogenesis is regarded as a hallmark in cancer development, and anti-angiogenic treatment is presently used in non-small cell lung cancer (NSCLC) patients. MicroRNAs (miRs) are small non-coding, endogenous, single stranded RNAs that regulate gene expression. As miRs are relatively stabile and measurable in both tissue and serum, they are potential prognostic and predictive markers. In this study we aimed to identify significant altered miRs related to angiogenesis in NSCLC
Project description:Angiogenesis is regarded as a hallmark in cancer development, and anti-angiogenic treatment is presently used in non-small cell lung cancer (NSCLC) patients. MicroRNAs (miRs) are small non-coding, endogenous, single stranded RNAs that regulate gene expression. As miRs are relatively stabile and measurable in both tissue and serum, they are potential prognostic and predictive markers. In this study we aimed to identify significant altered miRs related to angiogenesis in NSCLC From a large cohort of 335 NSCLC patients, paraffin-embedded samples from 10 patients with a short disease specific survival (DSS), 10 with a long DSS and 10 normal controls were analyzed.