Israeli David, Vu Hong Ai, Corre Guillaume, Miagoux Quentin, Richard Isabelle
Genethon, 91000 Evry, France.
Université Paris-Saclay, Univ Evry, Inserm, Généthon, Integrare Research Unit UMR_S951, 91000 Evry, France.
Noncoding RNA. 2022 Jun 30;8(4):48. doi: 10.3390/ncrna8040048.
It is now well-established that microRNA dysregulation is a hallmark of human diseases, and that aberrant expression of miRNA is not randomly associated with human pathologies but plays a causal role in the pathological process. Investigations of the molecular mechanism that links miRNA dysregulation to pathophysiology can therefore further the understanding of human diseases. The biological effect of miRNA is thought to be mediated principally by miRNA target genes. Consequently, the target genes of dysregulated miRNA serve as a proxy for the biological interpretation of miRNA dysregulation, which is performed by target gene pathway enrichment analysis. However, this method unfortunately often fails to provide testable hypotheses concerning disease mechanisms. In this paper, we describe a method for the interpretation of miRNA dysregulation, which is based on miRNA host genes rather than target genes. Using this approach, we have recently identified the perturbations of lipid metabolism, and cholesterol in particular, in Duchenne muscular dystrophy (DMD). The host gene-based interpretation of miRNA dysregulation therefore represents an attractive alternative method for the biological interpretation of miRNA dysregulation.
现已充分证实，微小RNA（miRNA）失调是人类疾病的一个标志，而且miRNA的异常表达并非随机地与人类病理相关，而是在病理过程中起因果作用。因此，对将miRNA失调与病理生理学联系起来的分子机制进行研究，有助于进一步理解人类疾病。miRNA的生物学效应被认为主要由miRNA靶基因介导。因此，失调miRNA的靶基因可作为对miRNA失调进行生物学解释的替代指标，这是通过靶基因通路富集分析来实现的。然而，不幸的是，这种方法常常无法提供关于疾病机制的可检验假设。在本文中，我们描述了一种基于miRNA宿主基因而非靶基因来解释miRNA失调的方法。利用这种方法，我们最近在杜氏肌营养不良症（DMD）中发现了脂质代谢的紊乱，尤其是胆固醇代谢的紊乱。因此，基于宿主基因对miRNA失调进行解释，是对miRNA失调进行生物学解释的一种有吸引力的替代方法。
