<p dir="ltr">Angiosarcoma (AS) is a rare, understudied cancer that arises from endothelial cells with an extremely poor prognosis. More research is necessary to understand AS pathogenesis, which will lead to the development of novel therapies to improve patient survival. Evidence from our lab highlights the importance of miRNAs in disease progression by demonstrating that endothelial cell-specific loss of mature miRNAs drives AS in mice. Furthermore, individual miRNAs have been characterized as tumor suppressors in AS. Taken together, this underscores the role of miRNAs in AS pathogenesis and suggests that they are an underexplored therapeutic strategy that could be efficacious in treating this cancer. Due to the evidence that miRNA loss is a driver of AS, we hypothesized that global miRNA enhancement would reduce cancer phenotypes. We interrogated this question through the use of a small molecule enhancer of RNAi, enoxacin. We found that enoxacin robustly reduced cancer phenotypes, particularly in AS models driven by miRNA loss, and that enoxacin increased the expression of mature tumor-suppressing miRNAs. We then thoroughly characterized miR-497 in angiosarcoma, demonstrating that miR-497 overexpression ablated tumor formation in mice through the regulation of a network of target genes. Furthermore, we identified <i>Vat1</i> as a novel target gene of miR-497, and found that genetic and pharmacologic inhibition of <i>Vat1</i> reduced cell migration in AS. Overall, this work further highlights the important roles miRNAs play in AS pathogenesis, and points toward miRNAs as an exciting therapy that should be explored further.</p>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/26343802 |
| Date | 22 July 2024 |
| Creators | Annaleigh Mae Powell (19185817) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/thesis/_b_MicroRNA_mediated_tumor_suppression_in_angiosarcoma_b_/26343802 |
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