Noncoding RNAs Associated with PPARs in Etiology of MAFLD as a Novel Approach for Therapeutics Targets.

IF 3.5 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

PPAR Research Pub Date : 2022-09-17 eCollection Date: 2022-01-01 DOI:10.1155/2022/6161694

Fatemeh Kazeminasab, Maryam Baharlooie, Kamran Ghaedi

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引用次数: 1

Abstract

Background: Metabolic associated fatty liver disease (MAFLD) is a complex disease that results from the accumulation of fat in the liver. MAFLD is directly associated with obesity, insulin resistance, diabetes, and metabolic syndrome. PPARγ ligands, including pioglitazone, are also used in the management of this disease. Noncoding RNAs play a critical role in various diseases such as diabetes, obesity, and liver diseases including MAFLD. However, there is no adequate knowledge about the translation of using these ncRNAs to the clinics, particularly in MAFLD conditions. The aim of this study was to identify ncRNAs in the etiology of MAFLD as a novel approach to the therapeutic targets.

Methods: We collected human and mouse MAFLD gene expression datasets available in GEO. We performed pathway enrichment analysis of total mRNAs based on KEGG repository data to screen the most potential pathways in the liver of MAFLD human subjects and mice model, and analyzed pathway interconnections via ClueGO. Finally, we screened disease causality of the MAFLD ncRNAs, which were associated with PPARs, and then discussed the role of revealed ncRNAs in PPAR signaling and MAFLD.

Results: We found 127 ncRNAs in MAFLD which 25 out of them were strongly validated before for regulation of PPARs. With a polypharmacology approach, we screened 51 ncRNAs which were causal to a subset of diseases related to MAFLD.

Conclusion: This study revealed a subset of ncRNAs that could help in more clear and guided designation of preclinical and clinical studies to verify the therapeutic application of the revealed ncRNAs by manipulating the PPARs molecular mechanism in MAFLD.

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与ppar相关的非编码rna在MAFLD病因学中作为治疗靶点的新途径。

背景:代谢性脂肪性肝病(MAFLD)是一种由肝脏脂肪堆积引起的复杂疾病。MAFLD与肥胖、胰岛素抵抗、糖尿病和代谢综合征直接相关。PPARγ配体，包括吡格列酮，也用于治疗这种疾病。非编码rna在多种疾病中发挥关键作用，如糖尿病、肥胖和包括MAFLD在内的肝脏疾病。然而，对于将这些ncrna应用于临床，特别是在mald条件下，还没有足够的知识。本研究的目的是鉴定MAFLD病因学中的ncrna，作为一种新的治疗靶点的方法。方法:收集GEO中可用的人和小鼠MAFLD基因表达数据集。我们基于KEGG库数据对总mrna进行通路富集分析，筛选MAFLD人类受试者和小鼠模型中最有潜力的通路，并通过ClueGO分析通路之间的相互关系。最后，我们筛选了与PPAR相关的MAFLD ncrna的疾病因果关系，然后讨论了揭示的ncrna在PPAR信号传导和MAFLD中的作用。结果:我们在MAFLD中发现了127个ncrna，其中25个在调控ppar方面得到了强有力的验证。通过多药理学方法，我们筛选了51种ncrna，这些ncrna与MAFLD相关的一组疾病有关。结论:本研究揭示了一个ncRNAs亚群，可以帮助更明确和指导临床前和临床研究的指定，通过操纵PPARs在MAFLD中的分子机制来验证所揭示的ncRNAs的治疗应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

PPAR Research MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

6.20

自引率

3.40%

发文量

审稿时长

12 months

期刊介绍： PPAR Research is a peer-reviewed, Open Access journal that publishes original research and review articles on advances in basic research focusing on mechanisms involved in the activation of peroxisome proliferator-activated receptors (PPARs), as well as their role in the regulation of cellular differentiation, development, energy homeostasis and metabolic function. The journal also welcomes preclinical and clinical trials of drugs that can modulate PPAR activity, with a view to treating chronic diseases and disorders such as dyslipidemia, diabetes, adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, and obesity.