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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
The p53-inducible long noncoding RNA TRINGS protects cancer cells from necrosis under glucose starvation
Muhammad Riaz Khan1, Shaoxun Xiang1, Zhiyin Song2
1CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for Excellence in Cell and Molecular Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science & Technology of China, Hefei, Anhui, China.
Abstract:
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-GSK3β-NF-κB 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.
Insights
The tumor suppressor p53 activates a new long noncoding RNA, TRINGS, during glucose starvation. TRINGS protects cancer cells with wild-type p53 from death by inhibiting necrotic signaling pathways.
Area of Science:
- Molecular Biology
- Cancer Research
- Cellular Stress Response
Background:
- The tumor suppressor p53 is crucial for preventing cancer.
- p53 can also protect tumor cells under stress.
- The role of p53-regulated long noncoding RNAs in this protection is unclear.
Purpose of the Study:
- To investigate the role of p53-regulated long noncoding RNAs in cancer cell survival under stress.
- To identify novel lncRNAs regulated by p53 during glucose starvation.
Main Methods:
- Analysis of p53-regulated gene expression under glucose starvation.
- Identification and characterization of a novel lncRNA (TRINGS).
- Investigation of TRINGS's mechanism of action involving STRAP and necrotic signaling pathways.
Main Results:
- p53 directly upregulates a novel lncRNA, TRINGS, under glucose starvation in human tumor cells.
- TRINGS inhibits the STRAP-GSK3β-NF-κB necrotic signaling pathway.
- TRINGS specifically responds to glucose deprivation, not other nutrient stresses.
Conclusions:
- p53-induced TRINGS is a key regulator of the necrotic pathway.
- TRINGS promotes the survival of cancer cells with wild-type p53 under glucose stress.
- This study reveals a novel mechanism of cancer cell adaptation to nutrient deprivation.
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