Distinct circular RNA expression profiles in pediatric ependymomas

Abstract

Pediatric ependymomas frequently develop in the cerebellum and are currently treated using non-specific therapies, in part, because few somatically mutated driver genes are present, and the underlying pathobiology is poorly described. Circular RNAs (circRNAs) constitute as a large class of primarily non-coding RNAs with important roles in tumorigenesis, but they have not been described in pediatric ependymomas. To advance our molecular understanding of ependymomas, we performed Next Generation Sequencing of rRNA-depleted total RNA of 10 primary ependymoma and three control samples. CircRNA expression patterns were correlated to disease stage, outcome, age, and gender. We found a profound global downregulation of circRNAs in ependymoma relative to control samples. Many differentially expressed circRNAs were discovered and circSMARCA5 and circ-FBXW7, which are described as tumor suppressors in glioma and glioblastomas in adults, were among the most downregulated. Moreover, patients with a dismal outcome clustered separately from patients with a good prognosis in unsupervised hierarchical cluster analyses. Next, NanoString nCounter experiments were performed, using a custom-designed panel targeting 66 selected circRNAs, on a larger cohort that also in

Digital multiplexed analysis of circular RNAs in FFPE and fresh non‐small cell lung cancer specimens

“…With a wide use for transcriptomic studies, nCounter has been recently adapted for the detection of circRNAs using a specific probe design where sequences span the circRNAs junction site [ 19 ]. On this regard, some authors have proved the benefits of this technology to study circRNA subcellular distribution [ 22 ], or elucidate the potential roles in skin [ 23 , 24 ] or brain diseases [ 25 ]. However, to date, no one has explored this platform in FFPE samples for the development of lung cancer signatures.…”

Role of Circular RNA in Brain Tumor Development

“…A vast group of mostly non-coding circular RNAs has important roles in tumorigenesis. Disease stage, outcome, age, and gender were associated with cirRNA patterns [ 42 ]. CircRNAs are a type of noncoding RNAs (ncRNAs) that have a continuous closed loop rather than 5′ caps and 3′ tails [ 21 , 43 ].…”

“…CircRNAs were numerous and even substantially produced in mammalian cells compared to the host gene’s linear RNA isoforms [ 21 ]. CircRNAs have emerged as a diverse class of endogenous RNAs with primarily non-coding functions essential for development and illness [ 42 ]. However, increased interest in circRNA has emerged in recent years as a result of their increasing operations in human biology [ 45 , 46 , 47 , 48 ].…”

“…However, increased interest in circRNA has emerged in recent years as a result of their increasing operations in human biology [ 45 , 46 , 47 , 48 ]. They have tissue-specific expression patterns and account for a sizable portion of cellular RNA, particularly in the brain [ 42 ]. CircRNAs have been implicated in miRNA response elements and gene expression regulation [ 21 ].…”

The emerging role of circular RNAs in common solid malignant tumors in children

“…This shows that circ-SKA3 and circ-DTL have key carcinogenic effects in the occurrence and development of medulloblastoma [ 43 ]. Ahmadov et al found that ependymoma specifically upregulated circRNA derived from RMST, LRBA, WDR78, DRC1 and BBS9 genes through Next Generation Sequencing, but their results still need experiments to prove [ 44 ].…”