Institute of Laboratory Medicine, University Hospital, LMU Munich, Munich, Germany.
Curr Opin Cardiol. 2023 May 1;38(3):179-192. doi: 10.1097/HCO.0000000000001041. Epub 2023 Mar 17.
Here, we review recent findings on the role of long noncoding RNAs (lncRNAs) in cardiovascular disease (CVD). In addition, we highlight some of the latest findings in lncRNA biology, providing an outlook for future avenues of lncRNA research in CVD.
Recent publications provide translational evidence from patient studies and animal models for the role of specific lncRNAs in CVD. The molecular effector mechanisms of these lncRNAs are diverse. Overall, cell-type selective modulation of gene expression is the largest common denominator. New methods, such as single-cell profiling and CRISPR/Cas9-screening, reveal additional novel mechanistic principles: For example, many lncRNAs establish RNA-based spatial compartments that concentrate effector proteins. Also, RNA modifications and splicing features can be determinants of lncRNA function.
lncRNA research is passing the stage of enumerating lncRNAs or recording simplified on-off expression switches. Mechanistic analyses are starting to reveal overarching principles of how lncRNAs can function. Exploring these principles with decisive genetic testing in vivo remains the ultimate test to discern how lncRNA loci, by RNA motifs or DNA elements, affect CVD pathophysiology.
本文综述了长链非编码 RNA（lncRNA）在心血管疾病（CVD）中的作用的最新研究发现。此外，我们还强调了 lncRNA 生物学的一些最新发现，为 CVD 中 lncRNA 研究的未来方向提供了展望。
最近的出版物提供了来自患者研究和动物模型的转化证据，证明了特定 lncRNA 在 CVD 中的作用。这些 lncRNA 的分子效应机制多种多样。总的来说，细胞类型选择性地调节基因表达是最大的共同点。单细胞分析和 CRISPR/Cas9 筛选等新方法揭示了其他新的机制原则：例如，许多 lncRNA 建立了基于 RNA 的空间隔室，集中了效应蛋白。此外，RNA 修饰和剪接特征可以决定 lncRNA 的功能。
lncRNA 研究正在超越列举 lncRNA 或记录简化的开/关表达开关的阶段。机制分析开始揭示 lncRNA 如何发挥作用的总体原则。用体内决定性的遗传测试来探索这些原则，仍然是辨别 lncRNA 基因座通过 RNA 基序或 DNA 元件如何影响 CVD 病理生理学的最终测试。
