Long noncoding RNA MEG3 activation of p53 mediates ischemic neuronal death in stroke
Abstract
Maternally expressed gene 3 (MEG3) is suggested to function as a long non-coding RNA (lncRNA) and to play roles in various human cancers. However, the functional properties of MEG3 in ischemic stroke remain unknown. Here, we report that expression of MEG3 is upregulated following ischemia in adult mice. Moreover, cerebral ischemia recruits p53 into the MEG3 complex in ischemic tissues. MEG3 directly binds with the p53 DNA binding domain (DBD) consisting of amino acids 271-282 (p53-DBD 271 - 282 ), which stimulates p53-mediated transactivation and mediates ischemic neuronal death. Administration of the membrane-permeable peptide inhibitor Tat-p53-DBD 271 - 282 uncouples p53 from MEG3 in vivo and protects against cerebral ischemic insults in vitro and in vivo. Our data demonstrate that MEG3 functions as a cell death promoter in ischemia and physically and functionally interacts with p53 to mediate ischemic damage. Intervention in the MEG3-p53 interaction presents a new target for the therapeutic treatment of ischemic insults.
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In the authors' previous study, they determined the expression and function of lncRNA MEG3 in cerebral ischemia.
“In our previous study, we first determined the expression and function of lncRNA MEG3 in cerebral ischemia24.”
From Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate ischemic neuronal death by targeting miR-21/PDCD4 signaling pathway (2017) · cites this paper as [24]
MEG3 interacts with p53 and activates p53-mediated transactivation to mediate ischemic neuronal death in stroke.
“Furthermore, MEG3 interacted with p53 and activated p53-mediated transactivation to mediate ischemic neuronal death in stroke24.”
From Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate ischemic neuronal death by targeting miR-21/PDCD4 signaling pathway (2017) · cites this paper as [24]
MEG3 functions as a cell death promoter in ischemia.
“Our previous study has revealed that lncRNA MEG3 functioned as a cell death promoter in ischemia24.”
From Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate ischemic neuronal death by targeting miR-21/PDCD4 signaling pathway (2017) · cites this paper as [24]
Ischemia alters cerebral MEG3 profiles in vitro and in vivo.
“Our previous study observed that ischemia altered cerebral MEG3 profiles in vitro and in vivo 24.”
From Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate ischemic neuronal death by targeting miR-21/PDCD4 signaling pathway (2017) · cites this paper as [24]
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References 37 · Cited by 142
- Authors
- Yan, H., Yuan, J., Gao, L., Rao, J., & Hu, J.
- Affiliations
- Renmin Hospital of Wuhan University (CN)
- Corresponding author
- Yuan, Jingping
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 337
- Pages
- 191-199
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2519202311
- Cited by
- 142
- References
- 37
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 11 · 2023: 8 · 2022: 17 · 2021: 18 · 2020: 24 · 2019: 25 · 2018: 20 · 2017: 13
- FWCI
- 8.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31600866)
- Independent Scientific Research Subject for Young Teachers of Wuhan University (2042016kf0116)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- MEG3, long non-coding RNA, p53, cerebral ischemia, ischemic stroke, neuronal cell death, p53 DNA-binding domain, protein-protein interaction, neuroprotection, stroke therapy targets
- MeSH terms
- Animals, Male, Mice, Inbred C57BL, Promoter Regions, Genetic, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, Cell Death, Stroke, Cell Line, Tumor, Cell Proliferation, RNA, Long Noncoding
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