Regulatory role of non-coding RNAs and their homeostasis by autophagy in the progression of atherosclerosis (B05)

动脉粥样硬化中自噬与非编码rna之间的相互作用尚不清楚。人类动脉粥样硬化的整体、单细胞和空间RNA测序发现了几种与自噬有潜在关联的失调的ncrna（目的1）。其中，HAND2-AS1与自噬相关介质相互作用。其在血管疾病进展中的功能作用将被研究（目的2）。此外，我们将通过先进的蛋白质组学和转录组学方法研究自噬诱导的ncRNA调控（目的3）。最终将在转基因小鼠模型中研究已鉴定的rna结合蛋白（如MEX3A）对动脉粥样硬化的贡献（目的4）。

The crosstalk between autophagy and non-coding RNAs in atherosclerosis remains unclear. Bulk, single-cell, and spatial RNA sequencing of human atherosclerosis identified several deregulated ncRNAs with potential relevance in autophagy (Aim 1). Among them, HAND2-AS1 interacts with autophagy-related mediators. Its functional role in vascular disease progression will be investigated (Aim 2). Further, we will study autophagy-induced ncRNA regulation through advanced proteomic and transcriptomic approaches (Aim 3). The contribution to atherosclerosis of identified RNA-binding proteins (e.g., MEX3A) will finally be studied in transgenic mice models (Aim 4).