Role of circular RNA in p53 mediated suppression of cancer development
Cells relying on mitochondrial metabolism may be impacted by copper-induced cell death, cuproptosis. . The role of p53, a tumor suppressor, in cuproptosis is not well understood.
The researchers discover that p53 induces the expression of a circular RNA, circFRMD4A. The authors show that circFRMD4A originates from the transcript of FRMD4A, which is transcriptionally activated by p53, and the formation of circFRMD4A is facilitated by the RNA-binding protein EWSR1.
They also demonstrate that circFRMD4A interacts with and inactivates the pyruvate kinase PKM2, leading to a decrease in lactate production and a redirection of glycolytic flux toward the tricarboxylic acid cycle.
This leads to an increase in mitochondrial metabolism and makes cancer cells more sensitive to cuproptosis, a form of cell death that relies on copper.
https://www.cell.com/molecular-cell/fulltext/S1097-2765(24)00918-3
