The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
EWSR1-induced circNEIL3 promotes glioma progression and exosome-mediated macrophage immunosuppressive polarization via stabilizing IGF2BP3
Open accessAbstract
Background: Gliomas are the most common malignant primary brain tumours with a highly immunosuppressive tumour microenvironment (TME) and poor prognosis. Circular RNAs (circRNA), a newly found type of endogenous noncoding RNA, characterized by high stability, abundance, conservation, have been shown to play an important role in the pathophysiological processes and TME remodelling of various tumours. Methods: CircRNA sequencing analysis was performed to explore circRNA expression profiles in normal and glioma tissues. The biological function of a novel circRNA, namely, circNEIL3, in glioma development was confirmed both in vitro and in vivo. Mechanistically, RNA pull-down, mass spectrum, RNA immunoprecipitation (RIP), luciferase reporter, and co-immunoprecipitation assays were conducted. Results: We identified circNEIL3, which could be cyclized by EWS RNA-binding protein 1(EWSR1), to be upregulated in glioma tissues and to correlate positively with glioma malignant progression. Functionally, we confirmed that circNEIL3 promotes tumorigenesis and carcinogenic progression of glioma in vitro and in vivo. Mechanistically, circNEIL3 stabilizes IGF2BP3 (insulin-like growth factor 2 mRNA binding protein 3) protein, a known oncogenic protein, by preventing HECTD4-mediated ubiquitination. Moreover, circNEIL3 overexpression glioma cells drives macrophage infiltration into the tumour microenvironment (TME). Finally, circNEIL3 is packaged into exosomes by hnRNPA2B1 and transmitted to infiltrated tumour associated macrophages (TAMs), enabling them to acquire immunosuppressive properties by stabilizing IGF2BP3 and in turn promoting glioma progression. Conclusions: This work reveals that circNEIL3 plays a nonnegligible multifaceted role in promoting gliomagenesis, malignant progression and macrophage tumour-promoting phenotypes polarization, highlighting that circNEIL3 is a potential prognostic biomarker and therapeutic target in glioma.
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1 retracted
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The Molecular Signatures Database Hallmark Gene Set Collection
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Spatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer
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Self-citationSumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs
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Cited by
Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer
Han, Q.-F., Li, W.-J., Hu, K.-S., Gao, J., Zhai, W.-L., Yang, J.-H., & Zhang, S.-J. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01671-0 · Cited by 678
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Metadata
- Authors
- Pan, Z., Zhao, R., Li, B., Qi, Y., Qiu, W., Guo, Q., Zhang, S., Zhao, S., Xu, H., Li, M., Gao, Z., Fan, Y., Xu, J., Wang, H., Wang, S., Qiu, J., Wang, Q., Guo, X., Deng, L., Zhang, P., Xue, H., & Li, G.
- Venue
- Molecular Cancer
- Published
- 2022-01-14
- Volume
- 21
- Issue
- 1
- Pages
- 16-16
- ISSN
- 1476-4598 (ISSN-L)
- OpenAlex
- W4205907754
- Cited by
- 312
- References
- 55
- FWCI
- 19.61
- Type
- journal article
- Language
- en
- Open access
- gold
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- Pan, Z., Zhao, R., Li, B., Qi, Y., Qiu, W., Guo, Q., Zhang, S., Zhao, S., Xu, H., Li, M., Gao, Z., Fan, Y., Xu, J., Wang, H., Wang, S., Qiu, J., Wang, Q., Guo, X., Deng, L., . . . Li, G. (2022). EWSR1-induced circNEIL3 promotes glioma progression and exosome-mediated macrophage immunosuppressive polarization via stabilizing IGF2BP3. Molecular Cancer. https://doi.org/10.1186/s12943-021-01485-6
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