The present study aimed to elucidate the function of lncRNA GARS1-DT in hypoxia-induced injury in ex-vivo cardiomyocytes and explore its underlying mechanism. Hypoxic injury was confirmed in H9C2 cells by the determination of cell viability, migration, invasion, and apoptosis. GARS1-DT expression was estimated in H9C2 cells after hypoxia. We then measured the effects of GARS1-DT knockdown on hypoxia-induced H9C2 cells. The interaction between GARS1-DT and miR-212-5p was also investigated. Hypoxia treatment led to cell damage in H9C2 cardiomyocytes, accompanied with the upregulation of GARS1-DT expression. Transfection of GARS1-DT siRNA remarkably attenuated hypoxia-induced injury by enhancing cell viability, migration and invasion, and reducing apoptosis. Furthermore, GARS1-DT served as an endogenous sponge for miR-212-5p, and its expression was negatively regulated by GARS1-DT. The effects of GARS1-DT knockdown on hypoxia-induced injury were significantly abrogated by miR-212-5p silence. Besides, suppression of GARS1-DT activated PI3K/AKT pathway in hypoxia-treated H9C2 cells, which were reversed by inhibition of miR-212-5p. Our findings demonstrated the novel molecular mechanism of GARS1-DT/miR-212-5p/PI3K/AKT axis on the regulation of hypoxia-induced myocardial injury in H9C2 cells, which might provide potential therapeutic targets for acute myocardial infarction (AMI) treatment.

中文翻译：

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抑制 GARS1-DT 通过海绵化 miR-212-5p 保护 H9C2 心肌细胞免受缺氧损伤。

本研究旨在阐明lncRNA GARS1-DT在离体心肌细胞缺氧损伤中的作用，并探讨其潜在机制。通过测定细胞活力、迁移、侵袭和凋亡，在 H9C2 细胞中证实了缺氧损伤。在缺氧后估计H9C2细胞中的GARS1-DT表达。然后我们测量了 GARS1-DT 敲低对缺氧诱导的 H9C2 细胞的影响。还研究了 GARS1-DT 和 miR-212-5p 之间的相互作用。缺氧处理导致 H9C2 心肌细胞的细胞损伤，伴随着 GARS1-DT 表达的上调。转染 GARS1-DT siRNA 通过增强细胞活力、迁移和侵袭以及减少细胞凋亡显着减轻缺氧诱导的损伤。此外，GARS1-DT 作为 miR-212-5p 的内源性海绵，其表达受 GARS1-DT 负调控。miR-212-5p 沉默显着消除了 GARS1-DT 敲低对缺氧诱导的损伤的影响。此外，GARS1-DT 的抑制激活了缺氧处理的 H9C2 细胞中的 PI3K/AKT 通路，这通过抑制 miR-212-5p 被逆转。我们的研究结果证明了 GARS1-DT/miR-212-5p/PI3K/AKT 轴调节 H9C2 细胞缺氧诱导的心肌损伤的新分子机制，这可能为急性心肌梗死 (AMI) 的治疗提供潜在的治疗靶点。