Zooming in on Long Non-Coding RNAs in Ewing Sarcoma Pathogenesis

Abstract

Ewing sarcoma (ES) is a rare aggressive cancer of bone and soft tissue that is mainly characterized by a reciprocal chromosomal translocation. As a result, about 90% of cases express the EWS-FLI1 fusion protein that has been shown to function as an aberrant transcription factor driving sarcomagenesis. ES is the second most common malignant bone tumor in children and young adults. Current treatment modalities include dose-intensified chemo- and radiotherapy, as well as surgery. Despite these strategies, patients who present with metastasis or relapse still have dismal prognosis, warranting a better understanding of treatment resistant-disease biology in order to generate better prognostic and therapeutic tools. Since the genomes of ES tumors are relatively quiet and stable, exploring the contributions of epigenetic mechanisms in the initiation and progression of the disease becomes inevitable. The search for novel biomarkers and potential therapeutic targets of cancer metastasis and chemotherapeutic drug resistance is increasingly focusing on long non-coding RNAs (lncRNAs). Recent advances in genome analysis by high throughput sequencing have immensely expanded and advanced our knowledge of lncRNAs. They are non-protein coding RNA species with multiple biological functions that have been shown to be dysregulated in many diseases and are emerging as crucial players in cancer development. Understanding the various roles of lncRNAs in tumorigenesis and metastasis would determine eclectic avenues to establish therapeutic and diagnostic targets. In ES, some lncRNAs have been implicated in cell proliferation, migration and invasion, features that make them suitable as relevant biomarkers and therapeutic targets. In this review, we comprehensively discuss known lncRNAs implicated in ES that could serve as potential biomarkers and therapeutic targets of the disease. Though some current reviews have discussed non-coding RNAs in ES, to our knowledge, this is the first review focusing exclusively on ES-associated lncRNAs.

Oncomeric Profiles of microRNAs as New Therapeutic Targets for Treatment of Ewing’s Sarcoma: A Composite Review

“…However, besides these miRs, there are some other long non-coding RNAs (lncRNAs) that have been shown to affect various aspects of carcinogenesis mostly through modulation of the function of cancer-associated miRs [96]. Deregulation of the miRs is a frequent feature of several illnesses.…”

The importance of fusion protein activity in Ewing sarcoma and the cell intrinsic and extrinsic factors that regulate it: A review

“…Non-coding RNAs (ncRNAs), including miRNAs and lncRNAs, are key regulators of transcription, translation, and signaling pathways. There is evidence that these ncRNAs are important epigenetic and transcriptional regulators of Ewing sarcoma oncogenesis ( 61 , 62 ). In addition, while EWS::FLI1 can modulate ncRNA expression, the fusion may in turn be regulated by these transcripts ( 48 , 63 ).…”

Study of Long Non-Coding RNA Tug1 Expression in Egyptian Colorectal Adenocarcinoma Patients

“…LncRNAs are nonprotein coding transcripts > 200 nucleotides, that have an epigenetic effect in CRC. 5 Taurine upregulated gene 1 (TUG1) is a lncRNA ($ 7.1 kb in length) located on chromosome 11. Previous studies expected TUG1 to be a new diagnostic biomarker and therapeutic target of certain cancers.…”