In:
Signal Transduction and Targeted Therapy, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2023-03-08)
Abstract:
In this study, we identified that a conserved circular RNA (circRNA) DICAR, which was downregulated in diabetic mouse hearts. DICAR had an inhibitory effect on diabetic cardiomyopathy (DCM), as the spontaneous cardiac dysfunction, cardiac cell hypertrophy, and cardiac fibrosis occurred in DICAR deficiency ( DICAR +/− ) mice, whereas the DCM was alleviated in DICAR-overexpressed DICAR Tg mice. At the cellular level, we found that overexpression of DICAR inhibited, but knockdown of DICAR enhanced the diabetic cardiomyocyte pyroptosis. At the molecular level, we identified that DICAR-VCP-Med12 degradation could be the underlying molecular mechanism in DICAR-mediated effects. The synthesized DICAR junction part (DICAR-JP) exhibited a similar effect to the entire DICAR. In addition, the expression of DICAR in circulating blood cells and plasma from diabetic patients was lower than that from health controls, which was consistent with the decreased DICAR expression in diabetic hearts. DICAR and the synthesized DICAR-JP may be drug candidates for DCM.
Type of Medium:
Online Resource
ISSN:
2059-3635
DOI:
10.1038/s41392-022-01306-2
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2023
detail.hit.zdb_id:
2886872-9
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