Epigenetic and Transcriptional Signaling in Ewing Sarcoma—Disease Etiology and Therapeutic Opportunities
Ewing sarcoma (EwS), a type of bone and soft tissue tumor, is mainly driven by the expression of the fusion protein EWSR1-FLI1. Upon binding to chromatin, EWSR1-FLI1 reprograms the epigenetic state, alters gene expression, and thus leads to tumorigenesis. Considerable studies have investigated the e...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/6/1325 |
| _version_ | 1797489740135530496 |
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| author | Mingli Li Chun-Wei Chen |
| author_facet | Mingli Li Chun-Wei Chen |
| author_sort | Mingli Li |
| collection | DOAJ |
| description | Ewing sarcoma (EwS), a type of bone and soft tissue tumor, is mainly driven by the expression of the fusion protein EWSR1-FLI1. Upon binding to chromatin, EWSR1-FLI1 reprograms the epigenetic state, alters gene expression, and thus leads to tumorigenesis. Considerable studies have investigated the epigenomic and transcriptomic profiling of EwS. Nevertheless, a comprehensive view of therapeutic targets is still lacking. This review discusses the epigenetic and transcriptional alterations reported in EwS. Specifically, we discuss the binding characteristics of EWSR1-FLI1 on chromatin, the mechanisms of EWSR1-FLI1 in reprograming epigenome, and EWSR1-FLI1-induced transcriptional alterations. Moreover, we summarize the chemical, RNAi, and CRISPR-cas9 high throughput screens conducted in EwS with the goal of assisting in the development of novel therapies to treat this aggressive disease. |
| first_indexed | 2024-03-10T00:20:58Z |
| format | Article |
| id | doaj.art-8e6212faac9042ae850eef29c65424e5 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T00:20:58Z |
| publishDate | 2022-06-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-8e6212faac9042ae850eef29c65424e52023-11-23T15:42:52ZengMDPI AGBiomedicines2227-90592022-06-01106132510.3390/biomedicines10061325Epigenetic and Transcriptional Signaling in Ewing Sarcoma—Disease Etiology and Therapeutic OpportunitiesMingli Li0Chun-Wei Chen1Department of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USADepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USAEwing sarcoma (EwS), a type of bone and soft tissue tumor, is mainly driven by the expression of the fusion protein EWSR1-FLI1. Upon binding to chromatin, EWSR1-FLI1 reprograms the epigenetic state, alters gene expression, and thus leads to tumorigenesis. Considerable studies have investigated the epigenomic and transcriptomic profiling of EwS. Nevertheless, a comprehensive view of therapeutic targets is still lacking. This review discusses the epigenetic and transcriptional alterations reported in EwS. Specifically, we discuss the binding characteristics of EWSR1-FLI1 on chromatin, the mechanisms of EWSR1-FLI1 in reprograming epigenome, and EWSR1-FLI1-induced transcriptional alterations. Moreover, we summarize the chemical, RNAi, and CRISPR-cas9 high throughput screens conducted in EwS with the goal of assisting in the development of novel therapies to treat this aggressive disease.https://www.mdpi.com/2227-9059/10/6/1325Ewing sarcomafusion proteinEWSR1-FLI1EWS-FLI1epigenetic regulationtranscriptional regulation |
| spellingShingle | Mingli Li Chun-Wei Chen Epigenetic and Transcriptional Signaling in Ewing Sarcoma—Disease Etiology and Therapeutic Opportunities Biomedicines Ewing sarcoma fusion protein EWSR1-FLI1 EWS-FLI1 epigenetic regulation transcriptional regulation |
| title | Epigenetic and Transcriptional Signaling in Ewing Sarcoma—Disease Etiology and Therapeutic Opportunities |
| title_full | Epigenetic and Transcriptional Signaling in Ewing Sarcoma—Disease Etiology and Therapeutic Opportunities |
| title_fullStr | Epigenetic and Transcriptional Signaling in Ewing Sarcoma—Disease Etiology and Therapeutic Opportunities |
| title_full_unstemmed | Epigenetic and Transcriptional Signaling in Ewing Sarcoma—Disease Etiology and Therapeutic Opportunities |
| title_short | Epigenetic and Transcriptional Signaling in Ewing Sarcoma—Disease Etiology and Therapeutic Opportunities |
| title_sort | epigenetic and transcriptional signaling in ewing sarcoma disease etiology and therapeutic opportunities |
| topic | Ewing sarcoma fusion protein EWSR1-FLI1 EWS-FLI1 epigenetic regulation transcriptional regulation |
| url | https://www.mdpi.com/2227-9059/10/6/1325 |
| work_keys_str_mv | AT minglili epigeneticandtranscriptionalsignalinginewingsarcomadiseaseetiologyandtherapeuticopportunities AT chunweichen epigeneticandtranscriptionalsignalinginewingsarcomadiseaseetiologyandtherapeuticopportunities |