The Circular RNA circNlgn Mediates Doxorubicin-Induced Cardiac Remodeling and Fibrosis
June 2022
in “
Molecular therapy. Nucleic acids
”
TLDR A specific RNA, circNlgn, contributes to heart damage and scarring caused by the cancer drug doxorubicin.
The study investigated the role of circular RNA circNlgn in mediating the cardiac side effects of doxorubicin, a chemotherapy drug. The researchers developed a transgenic mouse line overexpressing circNlgn and found that increased expression of circNlgn decreased cardiac function and induced cardiofibrosis. Silencing circNlgn decreased the effects of doxorubicin on cardiac cell activities and prevented doxorubicin-induced expression of fibrosis-associated molecules. The protein translated by circNlgn could bind and activate H2AX, leading to upregulation of several molecules. Silencing these molecules prevented doxorubicin-induced cardiomyocyte apoptosis, increased cardiomyocyte viability, decreased cardiac fibroblast proliferation, and inhibited collagen production. The study suggests that targeting circNlgn may help alleviate doxorubicin-induced cardiomyopathy and cardiac fibrosis.
