A major breakthrough in the Nature sub-journal! Activating cancer genes can regenerate the heart!

February 25, 2020 / / -- Researchers tried to turn off a gene that allows cancer to spread, only to make a surprise 180-degree turn.
by making the gene overactive and functional in the heart of mice, they trigger the regeneration of heart cells.
the power of this gene represents a significant advance in the first cure for heart disease, as adults' hearts are often unable to repair themselves if they are damaged.
Catherine Wilson, a pharmacologist at the University of Cambridge who led the study, said: "It's really exciting because scientists have been trying to multiply heart cells.
current treatments for heart disease do not reverse the degeneration of heart tissue - they can only slow the progression of the disease.
now, we've found a way to do this on the mouse model.
" Photo Source: Dr Cathy Wilson, University of Cambridge In Mammal Cells, cell cycles for self-replicating cells are tightly controlled.
cancer occurs when cells begin to replicate uncontrolled, and the Myc gene plays a key role in this process.
myc is known to be too active in most cancers, so research into the gene is one of the top priorities in cancer research.
recent studies have focused on trying to control Myc as a cancer treatment.
when researchers overactive Myc in mouse models, they saw its cancerous effects on organs, including the liver and lungs: large numbers of cells began to replicate within days.
but in the heart, nothing happened.
found that Myc-driven activity in myocardial cells is heavily dependent on the level of another protein in the cell called cell cycle protein T1, which is made from a gene called Ccnt1.
when the Ccnt1 and Myc genes are expressed at the same time, the heart enters a regenerative state and its cells begin to replicate.
results were published recently in Nature Communications.
Wilson said: "When both genes were overexposed in the heart muscle cells of adult mice at the same time, we saw a large number of cell replications, leading to a significant increase in the number of myocardial cells.
" heart failure affects about 23 million people worldwide each year, and there is no cure.
heart attack, an adult's heart loses up to 1 billion myocardial cells.
other organs of the body, the adult heart cannot regenerate itself, so these cells will never be replaced.
their loss reduces the strength of the heart and leads to scar formation, heart failure and eventual death.
using a new generation of sequencing techniques called ChiP, researchers were able to observe myc's role in heart cells.
Myc produces a protein called transcription factor, which binds to DNA in specific cells and activates gene expression.
, despite the success of protein binding, heart cells did not begin to replicate themselves because proteins do not activate gene expression.
lack of another protein in the heart that is critical to gene expression -- the cell cycle protein T1.
the protein to Myc's overactive cells causes the cells to begin to multiply.
image Source: Dr Cathy Wilson, University of Cambridge "The current treatment does not reverse the degeneration of heart tissue.
The inability of the heart to regenerate itself is a major clinical need that has not yet been met, and we found that even if Myc is turned on in the heart, there are no other tools that can make it work, which may be one of the reasons why heart cancer is so rare.
now that we know what's missing, we can add it and let the cells replicate.
"Overall, this study shows that the ability of tissue regeneration is closely related to the organization's responsiveness to Myc, while the organization's Myc responsiveness is tightly controlled by key components of the critical transcription mechanism, and Myc, together with this component, drives the biological regeneration process of the tissue."
addition, in addition to the key target genes that are widely present in various tissues, there are a large number of targets with tissue-specific levels of expression.
study focused on the liver and heart , two typical Myc-responsive renewable organs and non-renewable organs that Myc does not respond to.
but this study suggests that through deeper exploration, new knowledge and insights will be brought about in regenerative medicine and tumor susceptivity.
with the growth of the world's population and the increase in the incidence of heart failure, the cost of patient care is expected to increase significantly.
researchers hope to develop their findings into a gene therapy for heart disease.
"We wanted to use short-term, switchable techniques to activate Myc and cell cycle protein T1 in the heart."
so that we don't leave any genetic traces that might unanticly lead to cancer formation.
() References: Switch on a key cancer gene can provide first curative treatment for heart disease Bywater, M.J., Burkhart, D.L., Straube, J. et al. Reactivation of Myc transcription in the mouse heart unlocks its proliferative capacity. Nat Commun 11, 1827 (2020). https://doi.org/10.1038/s41467-020-15552-x.