当前位置: X-MOL 学术J. Mol. Cell. Cardiol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
LncRNA-Mhrt regulates cardiac hypertrophy by modulating the miR-145a-5p/KLF4/myocardin axis.
Journal of Molecular and Cellular Cardiology ( IF 4.9 ) Pub Date : 2020-01-23 , DOI: 10.1016/j.yjmcc.2019.12.013
Yao Xu 1 , Ying Luo 2 , Chen Liang 1 , Tongcun Zhang 1
Affiliation  

Cardiac hypertrophy is an early milestone of many heart diseases. LncRNAs often play a leading role in this process. However, its mechanism of action in cardiac hypertrophy has not been fully explained. In a previous study, we showed a new mode by which lncRNA-Mhrt inhibited cardiac hypertrophy by inhibiting myocardin. However, the underlying molecular mechanism remains unclear. This study aims to explore potential action modes of Mhrt in regulating the expression of myocardin in the process of cardiac hypertrophy. Here, we find that Mhrt reduces myocardin expression through KLF4 in vivo and in vitro. Meanwhile, Mhrt promotes the expression of KLF4 through direct binding to miR-145a-5p or inhibiting phosphorylation of KLF4 by forming a complex with KLF4 to prevent the binding of ERK and KLF4, thereby inhibiting myocardin expression and the development of myocardial hypertrophy. Taken together, our findings reveal a new pathway, Mhrt-KLF4-myocardin, that regulates cardiac hypertrophy and revealed additional possible action modes of Mhrt in the occurrence and development of cardiac hypertrophy. The new regulatory pathway serves as a potential therapeutic avenue for cardiac hypertrophy.

中文翻译:


LncRNA-Mhrt 通过调节 miR-145a-5p/KLF4/心肌素轴来调节心脏肥大。



心脏肥大是许多心脏病的早期里程碑。 LncRNA 通常在此过程中发挥主导作用。然而,其在心脏肥大中的作用机制尚未完全解释。在之前的研究中,我们展示了lncRNA-Mhrt通过抑制心肌素来抑制心脏肥大的新模式。然而,潜在的分子机制仍不清楚。本研究旨在探讨Mhrt在心肌肥厚过程中调节心肌素表达的潜在作用模式。在这里,我们发现 Mhrt 在体内和体外通过 KLF4 降低心肌素表达。同时,Mhrt通过直接结合miR-145a-5p促进KLF4的表达,或通过与KLF4形成复合物抑制KLF4的磷酸化,阻止ERK与KLF4的结合,从而抑制心肌素的表达和心肌肥厚的发生。总而言之,我们的研究结果揭示了一条新的途径——Mhrt-KLF4-心肌素,它可以调节心脏肥大,并揭示了 Mhrt 在心脏肥大的发生和发展中的其他可能的作用模式。新的调节途径可作为心脏肥大的潜在治疗途径。
更新日期:2020-01-24
down
wechat
bug