title: 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-DBD271-282), which stimulates p53-mediated transactivation and mediates ischemic neuronal death. Administration of the membrane-permeable peptide inhibitor Tat-p53-DBD271-282uncouples 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.
authors.affiliation: Department of Pathology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Pathology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China. Electronic address: yuanjingping2003@aliyun.com.
authors.forename: Jingping
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Pathology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China.
authors.forename: Likun
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Pathology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Rao
authors.affiliation: Department of Pathology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China.
authors.forename: Jichang
authors.initials: J
authors.lastname: Hu
mesh_terms: D000818:Animals; D016923:Cell Death; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D008297:Male; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D020521:Stroke / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D062085:RNA, Long Noncoding; D016159:Tumor Suppressor Protein p53
keywords: Tat-p53-DBD(271–282); ischemia; maternally expressed gene 3; neuronal death; p53