Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
J Investig Med. 2013 Mar;61(3):604-12. doi: 10.2310/JIM.0b013e3182819ac6.
MicroRNAs (miRNAs) participate in the regulation of cardiac hypertrophy. However, it remains largely unknown as to how miRNAs are integrated into the hypertrophic program. Ca/calmodulin-dependent protein kinase II (CaMKII) is a hypertrophic signaling marker. It is not yet clear which miRNAs can regulate CaMKIIδ.
In this study, we identified which miRNAs could regulate CaMKIIδ and how to regulate CaMKIIδ.
Through computational and expression analyses, miR-30b-5p was identified as a candidate regulator of CaMKIIδ. Quantitative expression analysis of hypertrophic models demonstrated significant down-regulation of miR-30b-5p compared with control groups. Luciferase reporter assay showed that miR-30b-5p could significantly inhibit the expression of CaMKIIδ. Moreover, through gain-of-function and loss-of-function approaches, we found miR-30b-5p could negatively regulate the expression of CaMKIIδ and miR-30b-5p was a regulator of cardiac hypertrophy.
Our study demonstrates that the expression of miR-30b-5p is down-regulated in cardiac hypertrophy, and restoration of its function inhibits the expression of CaMKIIδ, suggesting that miR-30b-5p may act as a hypertrophic suppressor.
MicroRNAs（miRNAs）参与心脏肥大的调控。然而，miRNAs 如何整合到肥大程序中，在很大程度上仍不清楚。Ca/钙调蛋白依赖性蛋白激酶 II（CaMKII）是一种肥大信号标志物。目前尚不清楚哪些 miRNAs 可以调节 CaMKIIδ。
本研究旨在确定哪些 miRNAs 可以调节 CaMKIIδ 及其调节方式。
通过计算和表达分析，鉴定出 miR-30b-5p 是 CaMKIIδ 的候选调节剂。与对照组相比，肥大模型的定量表达分析显示 miR-30b-5p 显著下调。荧光素酶报告基因检测表明，miR-30b-5p 可显著抑制 CaMKIIδ 的表达。此外，通过功能获得和功能丧失方法，我们发现 miR-30b-5p 可负向调节 CaMKIIδ 的表达，miR-30b-5p 是心脏肥大的调节因子。
本研究表明，miR-30b-5p 在心脏肥大中表达下调，恢复其功能可抑制 CaMKIIδ 的表达，提示 miR-30b-5p 可能作为一种肥大抑制因子发挥作用。
