Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA
【Abstract】Our previous studies have demonstrated that stable microRNAs (miRNAs) in mammalian serum and plasma are actively secreted from tissues and cells and can serve as a novel class of biomarkers for diseases, and act as signaling molecules in intercellular communication. Here, we report the surprising finding that exogenous plant miRNAs are present in the sera and tissues of various animals and that these exogenous plant miRNAs are primarily acquired orally, through food intake. MIR168a is abundant in rice and is one of the most highly enriched exogenous plant miRNAs in the sera of Chinese subjects. Functional studies in vitro and in vivo demonstrated that MIR168a could bind to the human/mouse low-density lipoprotein receptor adapter protein 1 (LDLRAP1) mRNA, inhibit LDLRAP1 expression in liver, and consequently decrease LDL removal from mouse plasma. These findings demonstrate that exogenous plant miRNAs in food can regulate the expression of target genes in mammals.
【中文摘要】我们早先的研究表明，稳定存在于哺乳动物血清与血浆的微小核糖核（miRNAs），从组织与细胞中活跃地分泌出来，是一类新型的疾病标志物可应用于疾病，发挥细胞间信号传递作用。这里，我们报告令人惊奇的发现，外源性的植物微小核糖核酸可以在多种动物的血清和组织内检测到，并且它们主要是通过进食的方式摄入体内的。其中编号为168a的植物微小核糖核酸（MIR168a）是一种稻米中富含的同时也是中国人血清中含量最为丰富的一种植物微小核糖核酸。体内和体外的功能性研究表明植物MIR168a可以结合人和小鼠的低密度脂蛋白受体衔接蛋白1（low density lipoprotein receptor adapter protein 1）的mRNA，从而抑制其在肝脏的表达，进而减缓低密度脂蛋白从血浆中的清除。这些发现证明食物中的外源性植物微小核糖核酸可以通过调控哺乳动物体内靶基因表达的方式影响摄食者的生理功能。
潜在意义
该发现从一种新的维度对于中国的古语“吃什么补什么（You are what you eat）”进行了科学解释。
