Cell Research advance online publication 20 September 2011;
Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA
Lin Zhang1,*, Dongxia Hou1,*, Xi Chen1,*, Donghai Li1,*, Lingyun Zhu1,2, 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
- 1Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China
- 2Department of Chemistry and Biology, School of Science, National University of Defense Technology, Changsha 410073, China;
- 3Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Tiyuanbei, Tianjin 300060, China
*These four authors contributed equally to this work.
Received 11 August 2011; Revised 23 August 2011; Accepted 26 August 2011; Published online 20 September 2011.
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.
microRNA; MIR168a; LDLRAP1; low-density lipoprotein; microvesicle; cross-kingdom