ORIGINAL ARTICLE

Cell Research (2011): 1-20
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Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA

Lin Zhang^1,*, Dongxia Hou^1,*, Xi Chen^1,*, Donghai Li^1,*, Lingyun Zhu^1,2, Yujing Zhang¹, Jing Li1, Zhen Bian¹, Xiangying Liang¹, Xing Cai¹, Yuan Yin¹, Cheng Wang¹, Tianfu Zhang¹, Dihan Zhu¹, Dianmu Zhang¹, Jie Xu¹, Qun Chen¹, Yi Ba³, Jing Liu¹, Qiang Wang¹, Jianqun Chen¹, Jin Wang¹, Meng Wang¹, Qipeng Zhang¹, Junfeng Zhang¹, Ke Zen¹ and Chen-Yu Zhang¹

Correspondence: Chen-Yu Zhang, E-mail: cyzhang@nju.edu.cn; Ke Zen, E-mail: kzen@nju.edu.cn; Junfeng Zhang, E-mail: jfzhang@nju.edu.cn *These four authors contributed equally to this work.

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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.

Cell Research advance online publication 20 September 2011; doi: 10.1038/cr.2011.158

Keywords: microRNA; MIR168a; LDLRAP1; low-density lipoprotein; microvesicle; cross-kingdom