دورية أكاديمية
Expression of circular RNAs in myelodysplastic neoplasms and their association with mutations in the splicing factor gene SF3B1
العنوان: | Expression of circular RNAs in myelodysplastic neoplasms and their association with mutations in the splicing factor gene SF3B1 |
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المؤلفون: | Iva Trsova, Andrea Hrustincova, Zdenek Krejcik, David Kundrat, Aleš Holoubek, Karolina Staflova, Lucie Janstova, Sarka Vanikova, Katarina Szikszai, Jiri Klema, Petr Rysavy, Monika Belickova, Monika Kaisrlikova, Jitka Vesela, Jaroslav Cermak, Anna Jonasova, Jiri Dostal, Jan Fric, Jan Musil, Michaela Dostalova Merkerova |
المصدر: | Molecular Oncology, Vol 17, Iss 12, Pp 2565-2583 (2023) |
بيانات النشر: | Wiley, 2023. |
سنة النشر: | 2023 |
المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
مصطلحات موضوعية: | circular RNA, myelodysplastic neoplasms, SF3B1, splicing, ZEB1, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
الوصف: | Mutations in the splicing factor 3b subunit 1 (SF3B1) gene are frequent in myelodysplastic neoplasms (MDS). Because the splicing process is involved in the production of circular RNAs (circRNAs), we investigated the impact of SF3B1 mutations on circRNA processing. Using RNA sequencing, we measured circRNA expression in CD34+ bone marrow MDS cells. We defined circRNAs deregulated in a heterogeneous group of MDS patients and described increased circRNA formation in higher‐risk MDS. We showed that the presence of SF3B1 mutations did not affect the global production of circRNAs; however, deregulation of specific circRNAs was observed. Particularly, we demonstrated that strong upregulation of circRNAs processed from the zinc finger E‐box binding homeobox 1 (ZEB1) transcription factor; this upregulation was exclusive to SF3B1‐mutated patients and was not observed in those with mutations in other splicing factors or other recurrently mutated genes, or with other clinical variables. Furthermore, we focused on the most upregulated ZEB1‐circRNA, hsa_circ_0000228, and, by its knockdown, we demonstrated that its expression is related to mitochondrial activity. Using microRNA analyses, we proposed miR‐1248 as a direct target of hsa_circ_0000228. To conclude, we demonstrated that mutated SF3B1 leads to deregulation of ZEB1‐circRNAs, potentially contributing to the defects in mitochondrial metabolism observed in SF3B1‐mutated MDS. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1878-0261 1574-7891 |
Relation: | https://doaj.org/toc/1574-7891; https://doaj.org/toc/1878-0261 |
DOI: | 10.1002/1878-0261.13486 |
URL الوصول: | https://doaj.org/article/cf124e1e1eda474f8d617a5629fc916b |
رقم الأكسشن: | edsdoj.f124e1e1eda474f8d617a5629fc916b |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 18780261 15747891 |
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DOI: | 10.1002/1878-0261.13486 |