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非酒精性脂肪性肝病患者lncRNA HCG18上调及其对胰岛素抵抗的调节作用

Upregulated lncRNA HCG18 in Patients with Non-Alcoholic Fatty Liver Disease and Its Regulatory Effect on Insulin Resistance.

作者信息

Xia Yu, Zhang Yanxia, Wang Huiyun

机构信息

Department of Health Comprehensive Geriatrics, Yidu Central Hospital of Weifang, Weifang, Shandong, People's Republic of China.

出版信息

Diabetes Metab Syndr Obes. 2021 Dec 3;14:4747-4756. doi: 10.2147/DMSO.S333431. eCollection 2021.

Abstract

PURPOSE

Non-alcoholic fatty liver disease (NAFLD) is a disease associated with genetic-environmental-metabolic stress, which severely damages the liver function of patients. This study aimed to explore the significance and probable functions of HCG18 in NAFLD.

PATIENTS AND METHODS

The expression of HCG18 and miR-197-3p was tested by qRT-PCR. The clinical signification of HCG18 was provided by the ROC curve and Pearson correlation. The corresponding mechanism was punctuated by the luciferase reporter assay and HFD-managed mice.

RESULTS

HCG18 expression was higher in the patients with NAFLD than in controls and in individuals with HOMA-IR score ≥2.5 than those with HOMA-IR score <2.5. HCG18 expression in NAFLD patients was related to BMI, HOMA-IR, ALT, FBG, TC, and TG. HCG18 showed satisfactory predictive accuracy in differentiating NAFLD patients and patients with HOMA-IR ≥2.5. Besides, HCG18 had protective impacts on blood glucose and fat deposition but not on body weight. MiR-197-3p is a direct gene of HCG18, and a reverse correlation was found between miR-197-3p and HCG18. Furthermore, miR-197-3p regulated the influence of HCG18 on insulin resistance and lipid accumulation.

CONCLUSION

Increased levels of HCG18 might be an alternate indicator for NAFLD patients. The HCG18-miR-197-3p axis exerted effects on the progression of fat sedimentation and glucose disorder in NAFLD.

摘要

目的

非酒精性脂肪性肝病(NAFLD)是一种与遗传-环境-代谢应激相关的疾病,严重损害患者的肝功能。本研究旨在探讨HCG18在NAFLD中的意义及可能的作用。

患者与方法

采用qRT-PCR检测HCG18和miR-197-3p的表达。通过ROC曲线和Pearson相关性分析提供HCG18的临床意义。通过荧光素酶报告基因检测和高脂饮食处理的小鼠来阐明相应机制。

结果

NAFLD患者中HCG18的表达高于对照组,且稳态模型评估的胰岛素抵抗(HOMA-IR)评分≥2.5的个体中HCG18的表达高于HOMA-IR评分<2.5的个体。NAFLD患者中HCG18的表达与体重指数(BMI)、HOMA-IR、谷丙转氨酶(ALT)、空腹血糖(FBG)、总胆固醇(TC)和甘油三酯(TG)相关。HCG18在区分NAFLD患者和HOMA-IR≥2.5的患者方面显示出令人满意的预测准确性。此外,HCG18对血糖和脂肪沉积有保护作用,但对体重没有影响。miR-197-3p是HCG18的直接靶基因,且miR-197-3p与HCG18呈负相关。此外,miR-197-3p调节了HCG18对胰岛素抵抗和脂质蓄积的影响。

结论

HCG18水平升高可能是NAFLD患者的一个替代指标。HCG18-miR-197-3p轴对NAFLD中脂肪沉积和糖代谢紊乱的进展发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce78/8651094/797ffb882978/DMSO-14-4747-g0001.jpg

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