In a collaborative effort, researchers of the labs of Jean-Christophe Marine (VIB-KULeuven) and Cédric Blanpain (ULB) have discovered an intriguing novel target for cancer therapy. NEAT1, a non-coding RNA present in the cell nucleus, seems to play an important role in the survival of highly dividing cells, especially cancer cells.
The new study revealed NEAT1 to be regulated by p53, perhaps the most widely known cancer suppressor gene. “When a cell is stressed or damaged, p53 will upregulate the expression of NEAT1,” explains PhD student Carmen Adriaens (VIB-KU Leuven). “This has two possible outcomes: the cell can either go into transient cell cycle arrest, giving it time to deal with the stress and repair the damage before continuing cell division. If the stress or damage is too high, however, p53 will instruct the cell to commit suicide and die.”
While this may suggest that NEAT1 is important to avoid cancer development, the opposite is true: “We expected NEAT1 to be a tumor suppressor, since it is regulated by p53,” says Prof. Jean-Christophe Marine (VIB-KU Leuven). “Instead, it turned out that NEAT1 helps cancer cells in growing opportunistically. They use the survival mechanisms put in place by NEAT1 to survive standard chemotherapeutics. Our research shows that cancer cells die more effectively after removing NEAT1. In other words: the loss of NEAT1 leads to increased chemosensitivity and cell death. Therefore, our findings can help develop new drugs targeting NEAT1 in order to kill cancer cells more effectively.”
p53 induces NEAT1 paraspeckles to modulate replication stress response and chemosensitivity, Adriaens, Standaert, et al., Nature Medicine 2016