Abstract
Ewing’s sarcoma (ES) is a pediatric sarcoma caused by a chromosomal translocation. Unlike in most cancers, the genomes of ES patients are very stable. The translocation product of the EWS-FLI1 fusion is most often the predominant genetic driver of oncogenesis, and it is pertinent to explore the role of epigenetic alterations in the onset and progression of ES. Several types of noncoding RNAs, primarily microRNAs and long noncoding RNAs, are key epigenetic regulators that have been shown to play critical roles in various cancers. The functions of these epigenetic regulators are just beginning to be appreciated in ES. Here, we performed a comprehensive literature review to identify these noncoding RNAs. We identified clinically relevant tumor suppressor microRNAs, tumor promoter microRNAs and long noncoding RNAs. We then explored the known interplay between different classes of noncoding RNAs and described the currently unmet need for expanding the noncoding RNA repertoire of ES. We concluded the review with a discussion of epigenetic regulation of ES via regulatory noncoding RNAs. These noncoding RNAs provide new avenues of exploration to develop better therapeutics and identify novel biomarkers.
Highlights
Ewing’s sarcoma (ES) primarily results in tumors of the bone or surrounding tissue and belongs to a larger group deemed Ewing’s sarcoma family tumors, which includes peripheral primitive neuroectodermal tumors that affect mostly soft tissues [1,2]
Most studies of tumor suppressor miRNA in ES focused on cell line assays and experiments with the following exceptions being noted: investigations into miR-21-3p and miR-34a used primary tumor data sets [53,57]; miRNA expression can decrease with disease progression for miR-34a, miR-139-5p and miR-584-5p [58,62]; miRNA expression at other times remain statistically equal across disease progression as in the case of miR-124-3p [62]
Noncoding RNAs can act as network modulators, the targets of unidentified long noncoding RNAs (lncRNAs)/circRNA sponge axes or players in yet unidentified cellular roles
Summary
Ewing’s sarcoma (ES) primarily results in tumors of the bone or surrounding tissue and belongs to a larger group deemed Ewing’s sarcoma family tumors, which includes peripheral primitive neuroectodermal tumors that affect mostly soft tissues [1,2]. In 90% of cases, the onset of tumorigenesis is the fusion of the Ewing sarcoma break point region 1 (EWSR1) and Friend leukemia intergenic (FLI1) genes following a reciprocal translocation event [6]. EWSR1 codes for an RNA-binding protein and is originally found on chromosome 22, while the FLI1 proto-oncogene codes for a transcription factor and is originally located on chromosome 11. Significant research initiatives have pursued the identification of pathways in which EWS-FLI1 is involved in and the role of non-genetic/epigenetic contributors to Biomedicines 2021, 9, 933. Biomedicines 2021, 9, 933 these events [10,11,12] Characterization of these epigenetic regulators, including noncoding. We present current understanding on the tumor suppressor roles of miRNAs, the oncogenic activity of both miRNAs and lncRNAs and the interplay between these two classes of ncRNAs in ES.
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