WTAP and m6A-modified circRNAs modulation during stress response in acute myeloid leukemia progenitor cells Article Swipe
Alessia Iaiza
,
Gilla Mazzanti
,
Frauke Goeman
,
Bianca Cesaro
,
Clelia Cortile
,
Giacomo Corleone
,
Claudia Tito
,
Francesca Liccardo
,
Luciana De Angelis
,
Vincenzo Petrozza
,
Silvia Masciarelli
,
Giovanni Blandino
,
Maurizio Fanciulli
,
Alessandro Fatica
,
Giulia Fontemaggi
,
Francesco Fazi
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1007/s00018-024-05299-9
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1007/s00018-024-05299-9
N 6 -methyladenosine (m 6 A) is one of the most prevalent and conserved RNA modifications. It controls several biological processes, including the biogenesis and function of circular RNAs (circRNAs), which are a class of covalently closed-single stranded RNAs. Several studies have revealed that proteotoxic stress response induction could be a relevant anticancer therapy in Acute Myeloid Leukemia (AML). Furthermore, a strong molecular interaction between the m 6 A mRNA modification factors and the suppression of the proteotoxic stress response has emerged. Since the proteasome inhibition leading to the imbalance in protein homeostasis is strictly linked to the stress response induction, we investigated the role of Bortezomib (Btz) on m 6 A regulation and in particular its impact on the modulation of m 6 A-modified circRNAs expression. Here, we show that treating AML cells with Btz downregulated the expression of the m 6 A regulator WTAP at translational level, mainly because of increased oxidative stress. Indeed, Btz treatment promoted oxidative stress, with ROS generation and HMOX-1 activation and administration of the reducing agent N-acetylcysteine restored WTAP expression. Additionally, we identified m 6 A-modified circRNAs modulated by Btz treatment, including circHIPK3, which is implicated in protein folding and oxidative stress regulation. These results highlight the intricate molecular networks involved in oxidative and ER stress induction in AML cells following proteotoxic stress response, laying the groundwork for future therapeutic strategies targeting these pathways.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1007/s00018-024-05299-9
- https://link.springer.com/content/pdf/10.1007/s00018-024-05299-9.pdf
- OA Status
- gold
- Cited By
- 6
- References
- 79
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4399924204
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4399924204Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1007/s00018-024-05299-9Digital Object Identifier
- Title
-
WTAP and m6A-modified circRNAs modulation during stress response in acute myeloid leukemia progenitor cellsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-06-23Full publication date if available
- Authors
-
Alessia Iaiza, Gilla Mazzanti, Frauke Goeman, Bianca Cesaro, Clelia Cortile, Giacomo Corleone, Claudia Tito, Francesca Liccardo, Luciana De Angelis, Vincenzo Petrozza, Silvia Masciarelli, Giovanni Blandino, Maurizio Fanciulli, Alessandro Fatica, Giulia Fontemaggi, Francesco FaziList of authors in order
- Landing page
-
https://doi.org/10.1007/s00018-024-05299-9Publisher landing page
- PDF URL
-
https://link.springer.com/content/pdf/10.1007/s00018-024-05299-9.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://link.springer.com/content/pdf/10.1007/s00018-024-05299-9.pdfDirect OA link when available
- Concepts
-
Myeloid leukemia, Progenitor cell, Myeloid, Cell biology, Progenitor, Biology, Leukemia, Fight-or-flight response, Modulation (music), Cancer research, Stem cell, Immunology, Genetics, Gene, Physics, AcousticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
6Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 4, 2024: 2Per-year citation counts (last 5 years)
- References (count)
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79Number of works referenced by this work
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-
10Other works algorithmically related by OpenAlex
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