Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fujian, China.
Laboratory Center, The Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, Fujian, China.
Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Oct;1864(10):1449-1457. doi: 10.1016/j.bbalip.2019.07.003. Epub 2019 Jul 19.
The contribution of ncRNAs, especially long non-coding RNAs (lncRNAs) to drug induced steatosis remains largely unknown. The aim of this study was to investigate the role of lncRNA ENST00000608794 in dexamethasone induced steatosis. We found that ENST00000608794 is expressed at higher levels in dexamethasone treated HepG2 cell, and ENST00000608794 can bind and be regulated by miR-15b-5p. Ectopic expression of ENST00000608794 enhanced steatosis and the protein expression of PDK4 which is a critical gene in lipid metabolism and also is a target of miR-15b-5p. However, the differentiated PDK4 expression between control and ectopic expression of ENST00000608794 was absence in the presence of miR-15b-5p inhibitor. Moreover, in dexamethasone treated HepG2 cell lines, ENST00000608794 increased whether with miR-15b-5p inhibitor treatment or not, while increase of PDK4 expression by dexamethasone was greatly compromised in the presence of miR-15b-5p mimic. Meanwhile, dexamethasone induced steatosis could be ameliorated by silencing ENST00000608794 or expressing miR-15b-5p. Taken together, the results suggested that ENST00000608794 plays an important role in dexamethasone induced steatosis, which was partly mediated by derepressing of PDK4 through competitively binding to miR-15b-5p.
非编码 RNA，尤其是长非编码 RNA（lncRNA），对药物诱导的脂肪变性的贡献在很大程度上仍不清楚。本研究旨在探讨 lncRNA ENST00000608794 在地塞米松诱导的脂肪变性中的作用。我们发现，ENST00000608794 在地塞米松处理的 HepG2 细胞中表达水平更高，并且 ENST00000608794 可以结合并受 miR-15b-5p 的调控。ENST00000608794 的异位表达增强了脂肪变性和 PDK4 的蛋白表达，PDK4 是脂质代谢中的关键基因，也是 miR-15b-5p 的靶基因。然而，在 miR-15b-5p 抑制剂存在的情况下，对照和 ENST00000608794 异位表达之间的 PDK4 表达差异不存在。此外，在地塞米松处理的 HepG2 细胞系中，ENST00000608794 的增加无论是否存在 miR-15b-5p 抑制剂，而 miR-15b-5p 模拟物的存在大大削弱了地塞米松诱导的 PDK4 表达增加。同时，沉默 ENST00000608794 或表达 miR-15b-5p 可改善地塞米松诱导的脂肪变性。总之，这些结果表明，ENST00000608794 在地塞米松诱导的脂肪变性中发挥重要作用，部分是通过与 miR-15b-5p 竞争结合来解除 PDK4 的抑制作用。
