Dandare Abdullahi, Khan Muhammad Jawad, Naeem Aisha, Liaquat Afrose
Department of Biosciences, COMSATS University Islamabad, Islamabad 45550, Pakistan.
Department of Biochemistry, Usmanu Danfodiyo University, Sokoto 840104, Nigeria.
Genes Dis. 2022 Jun 3;10(6):2393-2413. doi: 10.1016/j.gendis.2022.05.022. eCollection 2023 Nov.
Non-coding RNAs (ncRNAs) participate in the regulation of several cellular processes including transcription, RNA processing and genome rearrangement. The aberrant expression of ncRNAs is associated with several pathological conditions. In this review, we focused on recent information to elucidate the role of various regulatory ncRNAs i.e., micro RNAs (miRNAs), circular RNAs (circRNAs) and long-chain non-coding RNAs (lncRNAs), in metabolic diseases, e.g., obesity, diabetes mellitus (DM), cardiovascular diseases (CVD) and metabolic syndrome (MetS). The mechanisms by which ncRNAs participated in disease pathophysiology were also highlighted. miRNAs regulate the expression of genes at transcriptional and translational levels. circRNAs modulate the regulation of gene expression via miRNA sponging activity, interacting with RNA binding protein and polymerase II transcription regulation. lncRNAs regulate the expression of genes by acting as a protein decoy, miRNA sponging, miRNA host gene, binding to miRNA response elements (MRE) and the recruitment of transcriptional element or chromatin modifiers. We examined the role of ncRNAs in the disease pathogenesis and their potential role as molecular markers for diagnosis, prognosis and therapeutic targets. We showed the involvement of ncRNAs in the onset of obesity and its progression to MetS and CVD. miRNA-192, miRNA-122, and miRNA-221 were dysregulated in all these metabolic diseases. Other ncRNAs, implicated in at least three diseases include miRNA-15a, miRNA-26, miRNA-27a, miRNA-320, and miRNA-375. Dysregulation of ncRNAs increased the risk of development of DM and MetS and its progression to CVD in obese individuals. Hence, these molecules are potential targets to arrest or delay the progression of metabolic diseases.
非编码RNA(ncRNAs)参与多种细胞过程的调控,包括转录、RNA加工和基因组重排。ncRNAs的异常表达与多种病理状况相关。在本综述中,我们聚焦于最新信息,以阐明各种调控性ncRNAs,即微小RNA(miRNAs)、环状RNA(circRNAs)和长链非编码RNA(lncRNAs)在代谢性疾病,如肥胖、糖尿病(DM)、心血管疾病(CVD)和代谢综合征(MetS)中的作用。还强调了ncRNAs参与疾病病理生理学的机制。miRNAs在转录和翻译水平上调节基因表达。circRNAs通过miRNA海绵活性、与RNA结合蛋白相互作用以及聚合酶II转录调控来调节基因表达。lncRNAs通过充当蛋白质诱饵、miRNA海绵、miRNA宿主基因、与miRNA反应元件(MRE)结合以及招募转录元件或染色质修饰剂来调节基因表达。我们研究了ncRNAs在疾病发病机制中的作用及其作为诊断、预后和治疗靶点的分子标志物的潜在作用。我们展示了ncRNAs在肥胖症的发生及其向MetS和CVD进展中的作用。miRNA - 192、miRNA - 122和miRNA - 221在所有这些代谢性疾病中均失调。其他与至少三种疾病相关的ncRNAs包括miRNA - 15a、miRNA - 26、miRNA - 27a、miRNA - 320和miRNA - 375。ncRNAs的失调增加了肥胖个体患DM和MetS的风险及其向CVD进展的风险。因此,这些分子是阻止或延缓代谢性疾病进展的潜在靶点。