LncRNA NRON promotes tumorigenesis by enhancing MDM2 activity toward tumor suppressor substrates

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.

Nanotherapeutic approaches for delivery of long non-coding RNAs: an updated review with emphasis on cancer

“…By suppressing both P53-dependent and independent pathways, it contributes to tumor formation. 37 There was a co-regulatory relationship between LINC00106 and RPS19BP1 that inhibited p53 activity, promoting PCa cell proliferation and migration. 38 KRAS, TP53, CDKN2A, and SMAD4 are the four most frequently mutated genes associated with PaC, and they are considered to be the four major drivers of PaC.…”

Huaier suppresses cell viability, migration and invasion in human non-small cell lung cancer via lncRNA DLEU2/miR-212-5p/ELF3 axis

“…Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs that exceed 200 nucleotides in length. LncRNAs have been reported to act as oncogene or tumor suppressor in diverse biological processes [15][16][17]. With the development of RNA sequencing, more and more lncRNAs have been found to be dysregulated in lung cancer [18].…”