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Updated: Jul 22, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
A p53/LINC00324 positive feedback loop suppresses tumor growth by counteracting SET-mediated transcriptional
Ling Zhang1, Jun Zhang2, Xiaofeng Xuan3
1Center for Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, 68 Jiyang West Road, Suzhou 215600, China.
Abstract:
The p53 tumor suppressor exerts antitumor functions through its ability to regulate the transcription of its downstream targets. Long noncoding RNAs (lncRNAs) act as oncogenes or tumor suppressors implicated in tumorigenesis and tumor progression. Here, we identify the lncRNA LINC00324 (long intergenic noncoding RNA 00324) as a direct p53 transcriptional target. Knockdown of LINC00324 expression promotes tumor growth by reducing p53 transcriptional activity, whereas ectopic LINC00324 expression demonstrates a reverse effect. Notably, LINC00324 is present in the endogenous p53 complex in tumor cells and directly binds to the C-terminal domain of p53 in vitro. Mechanistically, LINC00324 enables p53 transactivation by competitively disrupting the p53-SET interaction, resulting in an increase of p300/CBP-mediated H3K18 and H3K27 acetylation on the p53 target promoters. Lower LINC00324 expression is associated with more aggressive disease status and predicts worse overall survival of patients with cancer. Our study identifies a p53/LINC00324 positive feedback loop that suppresses tumor growth by counteracting SET-mediated transcriptional repression.
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