Target gene regulatory network of miR-497 in angiosarcoma
Angiosarcoma (AS) is a vascular sarcoma that is highly aggressive and metastatic. Due to its rarity, treatment options for patients are limited, therefore more research is needed to identify possible therapeutic vulnerabilities. We previously found that endothelial deletion of Dicer1 drives AS development in mice. Given the role of DICER1 in canonical microRNA (miRNA) biogenesis, this suggests that miRNA loss may be important in AS development. After testing miRNAs previously suggested to have a tumor-suppressive role in AS, microRNA-497-5p (miR-497) suppressed cell viability most significantly. We also found that miR-497 expression led to significantly reduced cell migration and tumor formation. To understand the mechanism of miR-497 tumor suppression, we identified clinically relevant target genes using a combination of RNA-sequencing data in an AS cell line, expression data from AS patients, and target prediction algorithms. This work provides insight into the mechanisms of miR-497 and its target genes in AS pathogenesis. Overall design: To characterize the target gene network of miR-497, mouse angiosarcoma cell line, ADC106, was transfected with NC and miR-497 mimics, and RNA was extracted 3 days post-transfection. RNA-seq was performed to identify differential gene expression in response to miR-497 overexpression.