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Reciprocal modulation of long noncoding RNA EMS and p53 regulates tumorigenesis.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Jan 18; Vol. 119 (3). - Publication Year :
- 2022
-
Abstract
- p53 plays a central role in tumor suppression. Emerging evidence suggests long noncoding RNA (lncRNA) as an important class of regulatory molecules that control the p53 signaling. Here, we report that the oncogenic lncRNA E2F1 messenger RNA (mRNA) stabilizing factor (EMS) and p53 mutually repress each other's expression. EMS is negatively regulated by p53. As a direct transcriptional repression target of p53, EMS is surprisingly shown to inhibit p53 expression. EMS associates with cytoplasmic polyadenylation element-binding protein 2 (CPEB2) and thus, disrupts the CPEB2-p53 mRNA interaction. This disassociation attenuates CPEB2-mediated p53 mRNA polyadenylation and suppresses p53 translation. Functionally, EMS is able to exert its oncogenic activities, at least partially, via the CPEB2-p53 axis. Together, these findings reveal a double-negative feedback loop between p53 and EMS, through which p53 is finely controlled. Our study also demonstrates a critical role for EMS in promoting tumorigenesis via the negative regulation of p53.<br />Competing Interests: The authors declare no competing interest.<br /> (Copyright © 2022 the Author(s). Published by PNAS.)
- Subjects :
- Animals
Base Sequence
Cell Line, Tumor
Cell Proliferation genetics
Cellular Senescence genetics
Gene Expression Regulation, Neoplastic
HEK293 Cells
Humans
Male
Mice, Nude
Protein Biosynthesis
RNA, Long Noncoding genetics
RNA-Binding Proteins genetics
RNA-Binding Proteins metabolism
Transcription, Genetic
Mice
Carcinogenesis genetics
RNA, Long Noncoding metabolism
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 119
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 35022235
- Full Text :
- https://doi.org/10.1073/pnas.2111409119