LncRNA Tug1 relieves the steatosis of SelenoF-knockout hepatocytes via sponging miR-1934-3p,Cell Biology and Toxicology

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LncRNA Tug1 relieves the steatosis of SelenoF-knockout hepatocytes via sponging miR-1934-3p
Cell Biology and Toxicology ( IF 6.1 ) Pub Date : 2023-09-18 , DOI: 10.1007/s10565-023-09826-5
Wei Wang _{1,

2} , Zhiruo Miao ₂ , Xue Qi ₂ , Bing Wang ₂ , Qingqing Liu ₂ , Xu Shi ₂ , Shiwen Xu _{2,

3}

Affiliation

Metabolic dysfunction associated with fatty liver disease (MAFLD), always accompanied by disturbance of glucose and lipid metabolism, is becoming the most difficult obstacle in the next decades. In the current research, we uncover that the potent non-coding RNA Tug1, which is related to metabolic enzymes, regulates hepatocytes steatosis induced by sodium palmitate via miR-1934-3p absorbing. The knockdown of lncRNA-Tug1 distinctly rescues the increased expression level of glycolytic enzymes and fatty acid synthetase via releasing more mature miR-1934-3p in hepatocytes. Moreover, miR-1934-3p suppresses Selenoprotein F (SelenoF) through binding with the SelenoF 3′UTR effectors; importantly, we demonstrated that the deletion of SelenoF consistent with the lncRNA-Tug1’s effecting on metabolism enzymes. In the current paper, the interaction of Tug1/miR-1934-3p/SelenoF was verified by the dual-luciferase reporter system, and IRS1/AKT pathway possesses the essential role in glucolipid metabolism when SelenoF is deleted. We concluded that lncRNA Tug1 functioned as ceRNA to alleviate steatosis and glycolysis in hepatocytes of C57BL/6 through adsorbing miR-1934-3p to release SelenoF and triggering IRS/AKT pathway.

Graphical Abstract

The Tug1/miR-1934-3p/SelenoF constructed the ceRNA interact network
Selenoprotein F accelerates glucolipid metabolism via IRS1/AKT pathway
SelenoF-/- alleviates steatosis in mice liver

中文翻译：

LncRNA Tug1 通过海绵 miR-1934-3p 缓解 SelenoF 敲除肝细胞的脂肪变性

与脂肪肝病（MAFLD）相关的代谢功能障碍总是伴随着葡萄糖和脂质代谢紊乱，正在成为未来几十年最困难的障碍。在目前的研究中，我们发现与代谢酶相关的有效非编码RNA Tug1通过吸收miR-1934-3p来调节棕榈酸钠诱导的肝细胞脂肪变性。lncRNA-Tug1 的敲低通过在肝细胞中释放更成熟的 miR-1934-3p 明显地挽救了糖酵解酶和脂肪酸合成酶表达水平的增加。此外，miR-1934-3p 通过与 SelenoF 3'UTR 效应子结合来抑制硒蛋白 F (SelenoF)；重要的是，我们证明 SelenoF 的缺失与 lncRNA-Tug1 对代谢酶的影响一致。本文通过双荧光素酶报告系统验证了Tug1/miR-1934-3p/SelenoF的相互作用，并且当SelenoF缺失时，IRS1/AKT通路在糖脂代谢中具有重要作用。我们得出结论，lncRNA Tug1 作为 ceRNA 通过吸附 miR-1934-3p 释放 SelenoF 并触发 IRS/AKT 通路来减轻 C57BL/6 肝细胞的脂肪变性和糖酵解。