4.8 Article

The p53-inducible long noncoding RNA TRINGS protects cancer cells from necrosis under glucose starvation

Journal

EMBO JOURNAL
Volume 36, Issue 23, Pages 3483-3500

Publisher

WILEY
DOI: 10.15252/embj.201696239

Keywords

glucose starvation; necroptosis; p53; STRAP; TRINGS

Funding

  1. National Key R&D Program of China [2016YFC1302302]
  2. National Natural Science Foundation of China [81430065, 31371388]
  3. Hubei Natural Science Foundation [2014CFA023]
  4. Independent Scientific Research Project of Wuhan University

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The tumor suppressor p53 is activated in response to cellular stress to prevent malignant transformation. However, several recent studies have shown that p53 can play protective roles in tumor cell survival under adversity. Whether p53-regulated long noncoding RNAs are involved in this process remains to be fully understood. Here, we show that under glucose starvation condition, p53 directly upregulates a novel lncRNA named TRINGS (Tp53-regulated inhibitor of necrosis under glucose starvation) in human tumor cells. TRINGS binds to STRAP and inhibits STRAP-GSK3 beta-NF-kappa B necrotic signaling to protect tumor cells from cell death. Interestingly, TRINGS appears to respond to glucose starvation specifically, as it is not activated by serum, serine, or glutamine deprivation. Collectively, our findings reveal that p53-induced lncRNA TRINGS controls the necrotic pathway and contributes to the survival of cancer cells harboring wild-type p53 under glucose stress.

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