A highly abundant circular RNA from the RMST locus plays a role in posterior fossa ependymoma pathogenesis
Pediatric ependymoma (EPN) is one of the most common central nervous system (CNS) cancers in children often accompanied by bad prognosis. The circular RNA, circRMST, is known to be upregulated in posterior fossa (PF) EPN, but its functional role in the disease has not been explored. We found that circRMST is abundantly expressed in the cytoplasm of cancer cells in PF EPN patients. Moreover, knockdown of circRMST in EPN cancer stem cells induced differentiation-related pathways while the expression of cell cycle-related pathways was reduced, suggesting that it acts as an oncogene. We further validated these findings using flow cytometry-based cell cycle analysis and an in vitro serum-induced differentiation assay. Furthermore, we found that high circRMST expression and low promoter methylation levels are associated with poor prognosis. In conclusion, this study identifies circRMST as a novel oncogene in PF EPN. Overall design: Total RNA-seq 24h and 72h post circRMST knockdown (KD) in biological triplicates using two different dicer-substrate siRNA (DsiRNA) constructs (Negative control (NC), circRMST-KD1 and circRMST-KD2)