非酒精性脂肪肝患者外周血白细胞中长非编码 RNA MALAT1、GAS5、DANCR 和 TUG1 的表达水平

I. Kurbatova, A. Vasileva, L. Topchieva, O. Dudanova, A. A. Shopovskaya
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摘要

目的:比较分析长非编码RNA MALAT1、GAS5、DANCR、TUG1在健康人和非酒精性脂肪肝(肝脂肪变性、不同活动度的NASH、肝硬化)患者外周血白细胞(PBL)中的表达水平。材料和方法:我们对 106 名首次确诊为非酒精性脂肪肝的患者进行了检查:31名肝脏脂肪变性(LS)患者,64名NASH活动度为弱(WA)、中(MA)和高(HA)的患者,以及11名处于肝硬化(LC)阶段的患者。对照组由 30 名健康供体组成。通过 RT-PCR 法测定 PBL 中 TUG1、DANCR、MALAT1 和 GAS5 基因的 mRNA 水平。结果显示与LS相比,TUG1基因在NASH-WA患者PBL中的表达水平更高,而且随着NASH活动的增加,TUG1 mRNA在PBL中的表达水平呈上升趋势,这表明TUG1在PBL中的表达水平可作为微创诊断(区分LS和NASH-WA)和预后标志物(与NAFLD的进展有关)。对 lncRNA MALAT1 表达水平的分析表明,所有研究组之间没有显著差异。研究结果表明,GAS5 的表达水平具有复杂的动态变化:转录本水平在肝脏脂肪变性形成过程中升高,然后在向非酒精性脂肪肝转变过程中降低。研究表明,NASH-WA 患者 PBL 中 DANCR 的表达水平明显低于肝脏脂肪变性和 NASH-MA 患者。结论研究获得了非酒精性脂肪肝患者PBL中MALAT1、GAS5、DANCR、TUG1 lncRNA表达水平的新数据,表明可以将PBL中TUG1的表达水平作为非酒精性脂肪肝的微创诊断和预后标志物。还有研究表明,PBL 中的 DANCR mRNA 水平在区分 LS 和 NASH-WA 方面可能具有一定的诊断价值。
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Expression level of long non-coding RNA MALAT1, GAS5, DANCR and TUG1 in peripheral blood leukocytes of patients with non-alcoholic fatty liver disease
Purpose: Comparative analysis of the expression level of long non-coding RNAs MALAT1, GAS5, DANCR, TUG1 in peripheral blood leukocytes (PBL) of healthy people and patients with NAFLD (liver steatosis, NASH of varying activity, liver cirrhosis). Materials and methods: We examined 106 patients diagnosed with NAFLD for the first time: 31 patients with liver steatosis (LS), 64 patients with weak (WA), moderate (MA) and high (HA) NASH activity and 11 patients at the stage of liver cirrhosis (LC). The control group consisted of 30 healthy donors. The mRNA level of the TUG1, DANCR, MALAT1, GAS5 genes in PBL was determined by RT-PCR. Results: A higher level of expression of the TUG1 gene was registered in the PBL of patients with NASH-WA compared to LS, and a tendency was revealed to increase the level of TUG1 mRNA in the PBL with increasing NASH activity, which indicates the possibility of using the level of TUG1 expression in the PBL as a minimally invasive diagnostic (to distinguish between LS and NASH-WA) and a prognostic marker (with the progression of NAFLD). Analysis of the expression level of lncRNA MALAT1 showed no significant differences between all studied groups. Results were obtained indicating complex dynamics of the GAS5 expression level: the level of transcripts increases during the formation of liver steatosis and then decreases during the transition to NASH. It was shown that the level of DANCR expression in the PBL of patients with NASH-WA is significantly lower than in patients with liver steatosis and NASH-MA. Conclusion: New data were obtained on the expression level of the MALAT1, GAS5, DANCR, TUG1 lncRNAs in the PBL of patients with NAFLD, indicating the possibility of using the level of TUG1 expression in the PBL as a minimally invasive diagnostic and prognostic marker in NAFLD. It has also been shown that the level of DANCR mRNA in PBL may have some diagnostic value in distinguishing between LS and NASH-WA.
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