Desind Samuel Z, Bell Samira K, Davidson Zachary M, Lutz Carol S
Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers Biomedical and Health Sciences-New Jersey Medical School and Rutgers School of Graduate Studies, Newark, New Jersey, USA.
Wiley Interdiscip Rev RNA. 2023 Nov 23:e1828. doi: 10.1002/wrna.1828.
Long noncoding RNAs (lncRNAs) have emerged as critical regulators in numerous biological processes. The arachidonic acid (AA) metabolic pathway is a fundamental biochemical pathway responsible for the enzymatic conversion of AA, a 20-carbon omega-six polyunsaturated fatty acid, into a variety of potent lipid signaling molecules known as eicosanoids. Eicosanoids are produced through the cyclooxygenase and lipoxygenase arms of the AA pathway and have diverse biological roles in both healthy and disease states, including cancer and inflammatory diseases. Cyclooxygenase 2 (COX-2), the inducible, rate-limiting enzyme of the cyclooxygenase arm, produces two main forms of eicosanoids: prostaglandins and thromboxanes. AA metabolized through the lipoxygenase arm by the action of 5-lipoxygenase (ALOX5) produces eicosanoids known as leukotrienes. COX-2 and ALOX5 gene expression are regulated through many different lncRNAs and microRNA (miRNA)-mediated mechanisms. As previously reviewed, noncoding RNAs affect transcription, splicing, alternative polyadenylation, messenger RNA stability, translation, and miRNA regulation of COX-2 and ALOX5 (Lutz and Cornett, 2013, Wiley Interdisciplinary Reviews. RNA, 4(5), 593-605). This current review discusses the intricate roles of lncRNAs, including MALAT1, NEAT1, HOTAIR, PACER, and others, in modulating the AA pathway. In this review update, we will delve into advancements in our understanding of AA gene expression regulation. We will explore the mechanisms of lncRNAs and their associated miRNAs and proteins known to regulate key components of the AA signaling pathway. We will also discuss the therapeutic potential of targeting lncRNA-mediated regulation, with a focus on modulating COX-2 and ALOX5 activity and downstream eicosanoid production for applications in inflammatory and oncological conditions. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA in Disease and Development > RNA in Disease.
长链非编码RNA（lncRNA）已成为众多生物过程中的关键调节因子。花生四烯酸（AA）代谢途径是一条基本的生化途径，负责将20碳的ω-6多不饱和脂肪酸AA酶促转化为多种强效脂质信号分子，即类花生酸。类花生酸通过AA途径的环氧化酶和脂氧合酶分支产生，在健康和疾病状态（包括癌症和炎症性疾病）中具有多种生物学作用。环氧化酶2（COX-2）是环氧化酶分支的诱导性限速酶，产生两种主要形式的类花生酸：前列腺素和血栓素。通过5-脂氧合酶（ALOX5）作用经脂氧合酶分支代谢的AA产生称为白三烯的类花生酸。COX-2和ALOX5基因表达通过许多不同的lncRNA和微小RNA（miRNA）介导的机制进行调节。如先前综述所述，非编码RNA影响COX-2和ALOX5的转录、剪接、可变多聚腺苷酸化、信使RNA稳定性、翻译以及miRNA调节（Lutz和Cornett，2013年，《Wiley跨学科评论：RNA》，4(5)，593 - 605）。本综述讨论了lncRNA（包括MALAT1、NEAT1、HOTAIR、PACER等）在调节AA途径中的复杂作用。在本次综述更新中，我们将深入探讨我们对AA基因表达调控理解的进展。我们将探索lncRNA及其相关miRNA和蛋白质调节AA信号通路关键成分的机制。我们还将讨论靶向lncRNA介导调节的治疗潜力，重点是调节COX-2和ALOX5活性以及下游类花生酸产生，以用于炎症和肿瘤疾病。本文分类如下：调控RNA/RNA干扰/核糖开关>调控RNA 疾病与发育中的RNA>疾病中的RNA
