Cardiac hypertrophy at a decompensated state eventually leads to heart failure that mostly contributes to deaths globally. Dysregulated cardiac autophagy is a hallmark of a diseased heart, and a close contact between cardiac autophagy and cardiac hypertrophy is emerging. MicroRNAs (miRNAs) have been recently reported to be prominently implicated in cardiac hypertrophy through regulating cardiac autophagy. However, the role and function of miR302–367 clusters in cardiac autophagy and cardiac hypertrophy remain largely masked. Therefore, to investigate the performance of miR302–367 in cardiac hypertrophy, the specific in vitro hypertrophic model was established in H9c2 cells upon Ang II treatment. Consequently, we discovered a distinct inhibition on autophagy and a remarkable upregulation of miR302–367 expression in hypertrophic H9c2 cells. Besides, loss- and gain-of-function assays demonstrated miR302–367 inhibited autophagy and then aggravated cardiac hypertrophy. Mechanically, PTEN was predicted and confirmed as the shared target of miR302–367. Further, we recognized the apparent inactivation of PI3K/AKT/mTORC1 signaling in the face of miR302–367 suppression in Ang II-induced hypertrophic H9c2 cells. Moreover, co-treatment of PTEN inhibitor re-activated the PI3K/AKT/mTORC1 pathway, therefore counteracting the pro-autophagic and anti-hypertrophic effects of miR302–367 depletion on cardiomyocytes. These findings unveiled the pivotal role of the miR302–367 cluster in regulating cardiac autophagy and therefore modulating cardiac hypertrophy through PTEN/PI3K/AKT/mTORC1 signaling, indicating a promising therapeutic strategy for cardiac hypertrophy and even heart failure.

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处于失代偿状态的心脏肥大最终会导致心力衰竭，这主要是导致全球死亡的原因。心脏自噬失调是心脏疾病的标志，并且心脏自噬与心脏肥大之间的紧密联系正在形成。最近有报道说，通过调节心脏自噬，MicroRNA（miRNA）明显参与了心肌肥大。但是，miR302–367簇在心脏自噬和心脏肥大中的作用和功能仍然被掩盖。因此，为了研究miR302–367在心脏肥大中的表现，在Ang II处理后，在H9c2细胞中建立了特定的体外肥大模型。因此，我们发现了肥大性H9c2细胞中自噬的明显抑制和miR302–367表达的显着上调。除了，功能丧失和功能增强试验证明miR302-367抑制自噬，然后加重心脏肥大。在机械上，PTEN被预测并确认为miR302–367的共同靶标。此外，我们认识到在Ang II诱导的肥大性H9c2细胞中，面对miR302–367抑制，PI3K / AKT / mTORC1信号明显失活。此外，PTEN抑制剂的共同治疗可重新激活PI3K / AKT / mTORC1途径，因此抵消了miR302–367耗竭对心肌细胞的促自噬和抗肥大作用。这些发现揭示了miR302–367簇在调节心脏自噬并因此通过PTEN / PI3K / AKT / mTORC1信号调节心脏肥大中的关键作用，表明了心脏肥大甚至心力衰竭的有前途的治疗策略。

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