Systematic Analysis of Long Non-Coding RNA Genes in Nonalcoholic Fatty Liver Disease.
Systematic Analysis of Long Non-Coding RNA Genes in Nonalcoholic Fatty Liver Disease.
复制标题
非酒精性脂肪性肝病长链非编码RNA基因的系统分析
DOI：
10.3390/ncrna8040056
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发表时间：
2022-07-22
期刊：
影响因子：
4.3
通讯作者：
Uchida, Shizuka
中科院分区：
文献类型：
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作者：
Ilieva, Mirolyuba;Dao, James;Miller, Henry E;Madsen, Jens Hedelund;Bishop, Alexander J R;Kauppinen, Sakari;Uchida, Shizuka
肝脏是人类最大的实体器官，执行各种功能以维持生命。当受损时，肝脏中的细胞可以自我再生以维持正常的肝脏生理功能。然而，有些损伤是无法修复的，这就需要肝移植。肥胖率上升，西方饮食（即，肝脏疾病（富含加工碳水化合物和饱和脂肪）和心脏代谢疾病与肝脏疾病相关，包括非酒精性脂肪肝（NAFLD），这是一个集体术语，用于描述很少喝酒或不喝酒的人肝脏中脂肪的过度积累。令人担忧的是，NAFLD的患病率扩展到世界人口的25%，这迫切需要了解NAFLD的疾病机制。在这里，我们对NAFLD患者与健康和肥胖个体相比的已发表RNA测序（RNA-seq）数据进行了二次分析，以鉴定可能是NAFLD疾病机制的基础的长链非编码RNA（lncRNA）。与蛋白质编码基因类似，与健康和肥胖个体相比，NAFLD患者中许多lncRNA失调，这表明了解失调的lncRNA的功能可能有助于了解NAFLD的病理学。为了证明lncRNA在肝脏中的功能重要性，对一种NAFLD相关lncRNA LINC 01639进行了功能丧失实验，其显示其参与与细胞凋亡、TNF/TGF、细胞因子信号传导和生长因子相关的基因以及在NAFLD中上调的基因的调节。由于目前还没有专门针对肝脏，特别是NAFLD的lncRNA数据库，我们建立了一个网络数据库LiverDB，以进一步促进肝脏lncRNA的功能和机制研究。
The largest solid organ in humans, the liver, performs a variety of functions to sustain life. When damaged, cells in the liver can regenerate themselves to maintain normal liver physiology. However, some damage is beyond repair, which necessitates liver transplantation. Increasing rates of obesity, Western diets (i.e., rich in processed carbohydrates and saturated fats), and cardiometabolic diseases are interlinked to liver diseases, including non-alcoholic fatty liver disease (NAFLD), which is a collective term to describe the excess accumulation of fat in the liver of people who drink little to no alcohol. Alarmingly, the prevalence of NAFLD extends to 25% of the world population, which calls for the urgent need to understand the disease mechanism of NAFLD. Here, we performed secondary analyses of published RNA sequencing (RNA-seq) data of NAFLD patients compared to healthy and obese individuals to identify long non-coding RNAs (lncRNAs) that may underly the disease mechanism of NAFLD. Similar to protein-coding genes, many lncRNAs are dysregulated in NAFLD patients compared to healthy and obese individuals, suggesting that understanding the functions of dysregulated lncRNAs may shed light on the pathology of NAFLD. To demonstrate the functional importance of lncRNAs in the liver, loss-of-function experiments were performed for one NAFLD-related lncRNA, LINC01639, which showed that it is involved in the regulation of genes related to apoptosis, TNF/TGF, cytokine signaling, and growth factors as well as genes upregulated in NAFLD. Since there is no lncRNA database focused on the liver, especially NAFLD, we built a web database, LiverDB, to further facilitate functional and mechanistic studies of hepatic lncRNAs.
影响因子：
4.1
作者：
Bruce KD;Dobrinskikh E;Wang H;Rudenko I;Gao H;Libby AE;Gorkhali S;Yu T;Zsombok A;Eckel RH
通讯作者：
Eckel RH