Prolonged cardiac hypertrophy, a pathological compensatory response of the heart, finally leads to heart failure. Numerous studies have illustrated the vital roles of non-coding RNAs (ncRNAs) in cardiac hypertrophy. Here, we probed into the role and probable mechanism of microRNA-30e-5p (miR-30e-5p) in Angiotensin II (Ang–II)–stimulated hypertrophic cardiomyocytes. Intriguingly, the expression of hypertrophic markers, cell surface area and protein/DNA ratio were all reduced in Ang–II–induced hypertrophic cardiomyocytes when miR-30e-5p expression was augmented. Then, ADAM9 was screened out as the target of miR-30e-5p and ADAM9 overexpression rescued the effect of miR-30e-5p upregulation in Ang–II–treated cardiomyocytes. Moreover, we identified Kcnq1ot1 as the upstream of miR-30e-5p/ADAM9 axis and verified that Kcnq1ot1 aggrandized ADAM9 expression in Ang–II–treated cardiomyocytes through absorbing miR-30e-5p. Furthermore, rescue assays confirmed that ADAM9 up-regulation abrogated the repressive effect of Kcnq1ot1 depletion on Ang–II–induced cardiac hypertrophy. In conclusion, Kcnq1ot1 sequestered miR-30e-5p to release ADAM9 to facilitate cardiac hypertrophy, indicating that Kcnq1ot1 might be used as a potentially therapeutic target for cardiac hypertrophy.

长时间的心脏肥大，即心脏的病理性代偿反应，最终导致心力衰竭。大量研究表明，非编码RNA（ncRNA）在心脏肥大中起着至关重要的作用。在这里，我们探讨了microRNA-30e-5p（miR-30e-5p）在血管紧张素II（Ang-II）刺激的肥厚型心肌细胞中的作用和可能的机制。有趣的是，当miR-30e-5p表达增加时，Ang–II诱导的肥厚型心肌细胞中的肥厚标志物的表达，细胞表面积和蛋白质/ DNA比率均降低。然后，筛选出ADAM9作为miR-30e-5p的靶标，而ADAM9的过表达挽救了AngII治疗的心肌细胞中miR-30e-5p上调的作用。此外，我们确定Kcnq1ot1为miR-30e-5p / ADAM9轴的上游，并验证了Kcnq1ot1通过吸收miR-30e-5p增强了经Ang-II处理的心肌细胞中ADAM9的表达。此外，急救分析证实ADAM9的上调消除了Kcnq1ot1耗竭对Ang-II引起的心肌肥大的抑制作用。总之，Kcnq1ot1隔离miR-30e-5p以释放ADAM9以促进心脏肥大，表明Kcnq1ot1可能被用作心脏肥大的潜在治疗靶标。