Cardiac hypertrophy accompanied by maladaptive cardiac remodeling is the uppermost risk factor for the development of heart failure. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have various biological functions, and their vital role in the regulation of cardiac hypertrophy still needs to be explored. In this study, we demonstrated that lncRNA Plscr4 was upregulated in hypertrophic mice hearts and in angiotensin II (Ang II)–treated cardiomyocytes. Next, we observed that overexpression of Plscr4 attenuated Ang II-induced cardiomyocyte hypertrophy. Conversely, the inhibition of Plscr4 gave rise to cardiomyocyte hypertrophy. Furthermore, overexpression of Plscr4 attenuated TAC (transverse aortic constriction)-induced cardiac hypertrophy. Finally, we demonstrated that Plscr4 acted as an endogenous sponge of miR-214 and forced expression of Plscr4 downregulated miR-214 expression to promote Mfn2 and attenuate hypertrophy. In contrast, knockdown of Plscr4 upregulated miR-214 to induce cardiomyocyte hypertrophy. Additionally, luciferase assay showed that miR-214 was the direct target of Plscr4, and overexpression of miR-214 counteracted the anti-hypertrophy effect of Plscr4. Collectively, these findings identify Plscr4 as a negative regulator of cardiac hypertrophy in vivo and in vitro due to its regulation of the miR-214-Mfn2 axis, suggesting that Plscr4 might act as a therapeutic target for the treatment of cardiac hypertrophy and heart failure.

心脏肥大并伴有适应不良的心脏重塑是发生心力衰竭的最高危险因素。长的非编码RNA（lncRNA）和微小RNA（miRNA）具有多种生物学功能，它们在调节心脏肥大中的重要作用仍然有待探索。在这项研究中，我们证明了lncRNA Plscr4在肥厚小鼠心脏和血管紧张素II（Ang II）处理的心肌细胞中被上调。接下来，我们观察到Plscr4的过度表达减弱了Ang II诱导的心肌肥大。相反，对Plscr4的抑制导致心肌细胞肥大。此外，Plscr4的过表达减弱了TAC（横向主动脉收缩）引起的心脏肥大。最后，我们证明Plscr4充当miR-214的内源海绵，并强迫Plscr4的表达下调miR-214的表达以促进Mfn2并减轻肥大。相反，敲低Plscr4会上调miR-214诱导心肌细胞肥大。此外，萤光素酶检测显示miR-214是Plscr4的直接靶标，miR-214的过表达抵消了Plscr4的抗肥大作用。总的来说，这些发现确定Plscr4是心脏肥大的负调节剂 miR-214的过度表达抵消了Plscr4的抗肥大作用。总的来说，这些发现确定Plscr4是心脏肥大的负调节剂 miR-214的过度表达抵消了Plscr4的抗肥大作用。总的来说，这些发现确定Plscr4是心脏肥大的负调节剂由于其对miR-214-Mfn2轴的调控，它在体内和体外均具有特异性，这表明Plscr4可能充当心脏肥大和心力衰竭的治疗靶标。