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Oncogene-induced cardiac neoplasia shares similar mechanisms with heart regeneration in zebrafish

Pfefferli, C.; Bonvin, M.; Robatel, S.; Perler, J.; Koenig, D.; Jazwinska, A.

2020-12-15 cell biology
10.1101/2020.12.15.422853 bioRxiv
Show abstract

The human heart is a poorly regenerative organ and cardiac tumors are extremely rare. The zebrafish heart can restore its damaged myocardium through cardiomyocyte proliferation. Whether this endogenous capacity causes a susceptibility to neoplasia remains unknown. Here, we established a strategy to conditionally express the HRASG12V oncogene in zebrafish cardiomyocytes. The induction of this transgene in larvae or adult animals resulted in heart overgrowth with abnormal histology. The malformed ventricle displayed similar characteristics to the regenerative myocardium, such as enhanced cell-cycle entry, incomplete differentiation, reactivation of cardiac embryonic programs, expression of regeneration genes, oxidative metabolism changes, intramyocardial matrix remodeling and leucocyte recruitment. We found that oncogene-mediated cardiac tumorigenesis and cryoinjury-induced regeneration involve TOR signaling, as visualized by phosphorylation of its target ribosomal protein S6. The inhibition of TOR by rapamycin impaired regeneration and rescued from neoplasia. These findings demonstrate the existence of common mechanisms underlying the proliferative plasticity of zebrafish cardiomyocytes during advantageous organ restoration and detrimental tumorigenesis.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.