Long non-coding RNA (lncRNA) is known to be involved in a variety of diseases. However, the role of Gm4419 in hepatic ischemia-reperfusion (I/R) injury remains unknown. To study this, we first established a rat model of hepatic I/R, and a BRL-3A cell model of hypoxia-reoxygenation (H/R) for in vivo and in vitro studies. Staining with hematoxylin and eosin and hepatic injury scores were used to evaluate the degree of hepatic I/R injury. Cell apoptosis was assessed via staining with Edu, and with annexin V-FITC-propidium iodide assays. The interactions between Gm4419 and miR-455, as well as miR-455 and SOX6 were evaluated via luciferase reporter activity assays and RNA immunoprecipitation assays. In vivo, we found that Gm4419 was up-regulated in the rats subjected to I/R. Moreover, knockdown of Gm4419 alleviated the I/R-induced liver damage in the rats. In vitro, knockdown of Gm4419 alleviated H/R-induced apoptosis in BRL-3A cells. Interestingly, we found that miR-455 is a target of Gm4419, and Gm4419 regulates the expression of miR-455 via sponging. Furthermore, SOX6 was proven to be the target of miR-455. Finally, rescue experiments confirmed that knockdown of Gm4419 inhibits apoptosis by regulating miR-455 and SOX6 in H/R-treated BRL-3A cells. Therefore, our findings show that the lncRNA Gm4419 accelerates hepatic I/R injury by targeting the miR-455-SOX6 axis, which suggests a novel therapeutic target for hepatic I/R injury.

中文翻译：

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LncRNA Gm4419通过调节miR-455-SOX6轴诱导肝缺血再灌注损伤中的细胞凋亡。

长非编码RNA（lncRNA）已知与多种疾病有关。但是，Gm4419在肝缺血再灌注（I / R）损伤中的作用仍然未知。为了对此进行研究，我们首先建立了肝脏I / R大鼠模型，并建立了BRL-3A细胞缺氧-复氧（H / R）模型用于体内和体外研究。使用苏木精和曙红染色以及肝损伤评分来评估肝I / R损伤的程度。通过用Edu和膜联蛋白V-FITC-碘化丙啶染色来评估细胞凋亡。Gm4419和miR-455以及miR-455和SOX6之间的相互作用通过荧光素酶报道分子活性测定和RNA免疫沉淀测定进行了评估。在体内，我们发现Gm4419在接受I / R的大鼠中被上调。此外，击倒Gm4419减轻了I / R诱导的大鼠肝损伤。在体外，敲除Gm4419可减轻H / R诱导的BRL-3A细胞凋亡。有趣的是，我们发现miR-455是Gm4419的靶标，而Gm4419通过海绵调节miR-455的表达。此外，事实证明，SOX6是miR-455的靶标。最后，救援实验证实，敲除Gm4419可以通过调节H / R处理的BRL-3A细胞中的miR-455和SOX6来抑制细胞凋亡。因此，我们的发现表明，lncRNA Gm4419通过靶向miR-455-SOX6轴来加速肝I / R损伤，这提示了肝I / R损伤的新治疗靶点。Gm4419通过海绵调节miR-455的表达。此外，事实证明，SOX6是miR-455的靶标。最后，救援实验证实，敲除Gm4419可以通过调节H / R处理的BRL-3A细胞中的miR-455和SOX6来抑制细胞凋亡。因此，我们的发现表明，lncRNA Gm4419通过靶向miR-455-SOX6轴来加速肝I / R损伤，这提示了肝I / R损伤的新治疗靶点。Gm4419通过海绵调节miR-455的表达。此外，事实证明，SOX6是miR-455的靶标。最后，救援实验证实，敲除Gm4419可以通过调节经H / R处理的BRL-3A细胞中的miR-455和SOX6来抑制细胞凋亡。因此，我们的发现表明，lncRNA Gm4419通过靶向miR-455-SOX6轴来加速肝I / R损伤，这提示了肝I / R损伤的新治疗靶点。