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Updated: May 23, 2025
14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
9.5K
p53 activates circASCC3 to repress R-loops and enhance resistance to chemotherapy
Mingming Cao1,2, Yu Gan1,2, Yingdan Huang1,2
1Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Summary
The tumor suppressor p53 activates circASCC3, a circular RNA that resolves R-loops and protects cancer cells from chemotherapy by preventing DNA damage. This finding offers new insights into chemoresistance mechanisms.
Area of Science:
- Molecular Biology
- Cancer Research
- Genomics
Background:
- The tumor suppressor p53 plays a role in chemotherapy resistance by promoting DNA repair and genomic stability.
- Circular RNAs (circRNAs) are emerging as key regulators in various biological processes, including cancer.
Purpose of the Study:
- To investigate the role of p53-induced circular RNA circASCC3 in chemoresistance.
- To elucidate the mechanism by which circASCC3 confers resistance to chemotherapy.
Main Methods:
- Analysis of p53-mediated transcription of the ASCC3 gene.
- Identification of RNA-binding proteins interacting with circASCC3 precursors.
- Assessment of circASCC3's impact on cancer cell survival under DNA damage stress.
- Investigation of circASCC3's interaction with DDX5 and its effect on proteasomal degradation.
Main Results:
- p53 directly activates ASCC3 transcription, leading to circASCC3 production.
- p53 represses SFPQ expression, relieving its inhibition on circASCC3 formation.
- circASCC3 enhances cancer cell survival under DNA damage by binding DDX5 and preventing its degradation.
- This circASCC3-DDX5 interaction inhibits R-loop accumulation, conferring chemoresistance.
Conclusions:
- p53-induced circASCC3 promotes chemoresistance by resolving DNA damage-induced R-loops.
- The p53-circASCC3-DDX5 axis represents a novel mechanism contributing to tumor resistance to chemotherapy.
- Targeting this pathway may offer new therapeutic strategies for overcoming chemoresistance.
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