1. CircNCX1 modulates cardiomyocyte proliferation through promoting ubiquitination of BRG1.
- Author
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Yijian L, Weihan S, Lin Y, Heng Z, Yu W, Lin S, Shuo M, Mengyang L, and Jianxun W
- Subjects
- Animals, Rats, Sodium-Calcium Exchanger genetics, Cell Proliferation, DNA Helicases genetics, DNA Helicases metabolism, Myocytes, Cardiac metabolism, Myocytes, Cardiac cytology, Nuclear Proteins metabolism, Nuclear Proteins genetics, RNA, Circular metabolism, RNA, Circular genetics, Transcription Factors genetics, Transcription Factors metabolism, Ubiquitination
- Abstract
In mammal, the myocardium loss cannot be recovered spontaneously due to the negligible proliferation ability of mature mammalian cardiomyocyte. However, accumulated evidence has shown that terminally differentiated mammalian cardiomyocyte also has proliferation potency, which can be mediated by several mechanisms. Here, we reported that circNCX1, the most abundant circular RNA in mammalian hearts, can affect the proliferation of murine cardiomyocytes. The level of circNCX1 is significantly elevated during heart development. Forced expression of circNCX1 inhibits cardiomyocyte proliferation, while silencing of endogenous circNCX1 in cardiomyocyte shows reversed effect in vitro. Mechanistically, circNCX1 functions via negatively regulating transcription activator BRG1. It bridges BRG1 and FBXW7 to enhance the ubiquitination and degradation of BRG1, decreasing the expression of BMP10 to lead cell cycle arrest. In summary, our study first revealed that circNCX1 is a modulator of cardiomyocyte proliferation., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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