Encarnação Marisa, David Hugo, Coutinho Maria Francisca, Moreira Luciana, Alves Sandra
Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano 321, 4000-055 Porto, Portugal.
Center for the Study of Animal Science-Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto, CECA-ICETA, University of Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal.
Biomedicines. 2023 Sep 23;11(10):2615. doi: 10.3390/biomedicines11102615.
Lipids are essential for cellular function and are tightly controlled at the transcriptional and post-transcriptional levels. Dysregulation of these pathways is associated with vascular diseases, diabetes, cancer, and several inherited metabolic disorders. MicroRNAs (miRNAs), in particular, are a family of post-transcriptional gene repressors associated with the regulation of many genes that encode proteins involved in multiple lipid metabolism pathways, thereby influencing their homeostasis. Thus, this class of non-coding RNAs (ncRNAs) has emerged as a promising therapeutic target for the treatment of lipid-related metabolic alterations. Most of these miRNAs act at an intracellular level, but in the past few years, a role for miRNAs as intercellular signaling molecules has also been uncovered since they can be transported in bodily fluids and used as potential biomarkers of lipid metabolic alterations. In this review, we point out the current knowledge on the miRNA signature in a lysosomal storage disorder associated with lipid dysfunction, Niemann-Pick type C, and discuss the potential use of miRNAs as biomarkers and therapeutic targets for RNA-based therapies.
脂质对于细胞功能至关重要,并且在转录和转录后水平受到严格调控。这些途径的失调与血管疾病、糖尿病、癌症以及几种遗传性代谢紊乱有关。特别是微小RNA(miRNA),是一类转录后基因抑制因子,与许多编码参与多种脂质代谢途径的蛋白质的基因调控相关,从而影响它们的稳态。因此,这类非编码RNA(ncRNA)已成为治疗脂质相关代谢改变的有前景的治疗靶点。这些miRNA大多在细胞内发挥作用,但在过去几年中,由于它们可以在体液中运输并用作脂质代谢改变的潜在生物标志物,miRNA作为细胞间信号分子的作用也被发现。在本综述中,我们指出了与脂质功能障碍相关的溶酶体贮积症——尼曼-皮克C型病中miRNA特征的当前知识,并讨论了miRNA作为生物标志物的潜在用途以及基于RNA疗法的治疗靶点。