The E3 ligase MDM2 promotes tumor growth and progression by inducing ubiquitin-mediated degradation of P53 and other tumor-suppressing proteins. Here, we identified an MDM2-interacting lncRNA NRON, which promotes tumor formation by suppressing both P53-dependent and independent pathways. NRON binds to MDM2 and MDMX (MDM4) via two different stem-loops, respectively, and induces their heterogenous dimerization, thereby enhancing the E3 ligase activity of MDM2 toward its tumor-suppressing substrates, including P53, RB1, and NFAT1. NRON knockdown dramatically inhibits tumor cell growth in vitro and in vivo. More importantly, NRON overexpression promotes oncogenic transformation by inducing anchorage-independent growth in vitro and facilitating tumor formation in immunocompromised mice. Clinically, NRON expression is significantly associated with poor clinical outcome in breast cancer patients. Together, our data uncover a pivotal role of lncRNA that induces malignant transformation of epithelial cells by inhibiting multiple tumor suppressor proteins.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10425849 | PMC |
| http://dx.doi.org/10.15252/embj.2022112414 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Involvement of NRON and TUG1 long noncoding RNAs in inflammation and the pathogenesis of EAE.
Nucleosides Nucleotides Nucleic Acids
December 2023
Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.
There is growing evidence that the long noncoding RNAs (lncRNAs) contribute to the pathogenesis of various neurodegenerative diseases such as multiple sclerosis (MS). The role of lncRNAs nuclear repressor of NFAT (NRON) and Taurine up-regulated 1 (TUG1) in the inflammatory processes occurring in the experimental autoimmune encephalomyelitis (EAE) model of MS is yet to be investigated. Transcript levels of and in acute and chronic phases of EAE and cultured macrophages as well as the correlation between and expression with inflammatory cytokines, were evaluated in this study.
View Article and Find Full Text PDFDownregulated nuclear lncRNA NRON inhibits SHP2/Wnt/β-catenin signaling and cardiomyocyte differentiation during the development of Tetralogy of Fallot.
Genes Dis
May 2023
Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai 200011, China.
LncRNA NRON promotes tumorigenesis by enhancing MDM2 activity toward tumor suppressor substrates.
EMBO J
August 2023
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
The E3 ligase MDM2 promotes tumor growth and progression by inducing ubiquitin-mediated degradation of P53 and other tumor-suppressing proteins. Here, we identified an MDM2-interacting lncRNA NRON, which promotes tumor formation by suppressing both P53-dependent and independent pathways. NRON binds to MDM2 and MDMX (MDM4) via two different stem-loops, respectively, and induces their heterogenous dimerization, thereby enhancing the E3 ligase activity of MDM2 toward its tumor-suppressing substrates, including P53, RB1, and NFAT1.
View Article and Find Full Text PDFLncRNA Nron deficiency protects mice from diet-induced adiposity and hepatic steatosis.
Metabolism
November 2023
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Huazhong University of Science and Technology, Wuhan, China; Hubei Clinical Research Center of Metabolic and Cardiovascular Disease, Huazhong University of Science and Technology, Wuhan, China. Electronic address:
Obesity, as a worldwide healthcare problem, has attracted more and more attention. Here we identify a long non-coding RNA NRON, which is highly conserved across species, as an important regulator of glucose/lipid metabolism and whole-body energy expenditure. Depletion of Nron leads to metabolic benefits in DIO (diet-induced obesity) mice, including reduced body weight and fat mass, improved insulin sensitivity and serum lipid parameters, attenuated hepatic steatosis and enhanced adipose function.
View Article and Find Full Text PDFPSMD11 modulates circadian clock function through PER and CRY nuclear translocation.
PLoS One
March 2023
Divisions of Human Genetics and Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
The molecular circadian clock is regulated by a transcriptional translational feedback loop. However, the post-translational control mechanisms are less understood. The NRON complex is a large ribonucleoprotein complex, consisting of a lncRNA and several proteins.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!