长非编码RNA及其在塑造和调节花生四烯酸代谢中的复杂作用：学会爱上（不是真正的）垃圾,WIREs RNA

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长非编码RNA及其在塑造和调节花生四烯酸代谢中的复杂作用：学会爱上（不是真正的）垃圾
WIREs RNA ( IF 6.4 ) Pub Date : 2023-11-23 , DOI: 10.1002/wrna.1828
Samuel Z Desind ₁ , Samira K Bell ₁ , Zachary M Davidson ₁ , Carol S Lutz ₁

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长非编码 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生化途径，负责将 AA（一种 20 碳 omega-6 多不饱和脂肪酸）酶促转化为多种有效的脂质信号分子（称为类二十烷酸）。类二十烷酸是通过 AA 途径的环氧合酶和脂氧合酶臂产生的，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。环氧合酶 2 (COX-2) 是环氧合酶臂的诱导型限速酶，可产生两种主要形式的类二十烷酸：前列腺素和血栓素。AA 在 5-脂氧合酶 (ALOX5) 的作用下通过脂氧合酶臂代谢，产生称为白三烯的类二十烷酸。COX-2 和 ALOX5 基因表达通过许多不同的 lncRNA 和 microRNA (miRNA) 介导的机制进行调节。如前所述，非编码 RNA 影响 COX-2 和 ALOX5 的转录、剪接、选择性多腺苷酸化、信使 RNA 稳定性、翻译以及 miRNA 调节（Lutz 和 Cornett，2013，Wiley跨学科评论。RNA , 4 (5), 593–605 ）。本篇综述讨论了 lncRNA（包括 MALAT1、NEAT1、HOTAIR、PACER 等）在调节 AA 通路中的复杂作用。在这篇综述更新中，我们将深入探讨我们对 AA 基因表达调控的理解的进展。我们将探索已知调节 AA 信号通路关键成分的 lncRNA 及其相关 miRNA 和蛋白质的机制。我们还将讨论针对 lncRNA 介导的调节的治疗潜力，重点是调节 COX-2 和 ALOX5 活性以及下游类二十烷酸的产生，以应用于炎症和肿瘤疾病。

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Long noncoding RNAs and their complex role in shaping and regulating arachidonic acid metabolism: Learning to love the (not-really) junk

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.

更新日期：2023-11-24

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