LncRNA NRON promotes tumorigenesis by enhancing MDM2 activity toward tumor suppressor substrates.
EMBO J
; 42(16): e112414, 2023 08 15.
Article
em En
| MEDLINE
| ID: mdl-37382239
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas c-mdm2
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RNA Longo não Codificante
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article