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Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA
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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.
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“A consequent disruption of general metabolism in the GMO cannot be excluded, which could lead, for example, to the production of other potentially active compounds such as miRNAs (Zhang et al., 2012) or leukotoxin diols (Markaverich et al., 2005).”
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Metadata
- Authors
- Zhang, L., Hou, D., Chen, X., Li, D., Zhu, L., Zhang, Y., Li, J., Bian, Z., Liang, X., Cai, X., Yin, Y., Wang, C., Zhang, T., Zhu, D., Zhang, D., Xu, J., Chen, Q., Ba, Y., Liu, J., Wang, Q., Chen, J., Wang, J., Wang, M., Zhang, Q., Zhang, J., Zen, K., & Zhang, C.-Y.
- Affiliations
- State Key Laboratory of Pharmaceutical Biotechnology (CN)
- National University of Defense Technology (CN)
- Tianjin Medical University Cancer Institute and Hospital (CN)
- Corresponding author
- Zhang, Junfeng
- Zen, Ke
- Zhang, Chen-Yu
- ORCID
- Venue
- Cell Research
- Published
- 2011-09-20
- Volume
- 22
- Issue
- 1
- Pages
- 107-126
- ISSN
- 1001-0602 (ISSN-L)
- 1748-7838
- PMC
- PMC3351925
- OpenAlex
- W2165374397
- Cited by
- 1,216
- References
- 56
- Citations by year
- 2026: 77 · 2025: 89 · 2024: 95 · 2023: 94 · 2022: 86 · 2021: 96 · 2020: 85 · 2019: 76 · 2018: 66 · 2017: 72 · 2016: 78 · 2015: 82 · 2014: 77 · 2013: 84 · 2012: 55
- FWCI
- 23.66
- Type
- journal article
- Language
- en
- Update notices
- erratum (2011-11-08)
- Open access
- bronze
- doi.org
- Locations
- Cell Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research Institute
- Yale University
- National Natural Science Foundation of China (30771036, 973 Program, 30890032, 90608010, 30772484, 31000323, 30890044, 31071232, 30725008, 90813035)
- Government of Jiangsu Province
- Natural Science Foundation of Jiangsu Province (BK2008021)
- National Institutes of Health
- National Key Research and Development Program of China (2006CB503909)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- LDLRAP1, cross-kingdom regulation, serum microRNA, rice, liver, intercellular communication, biomarkers
- MeSH terms
- Adult, Animals, Diet, Female, Gene Expression Regulation, Humans, Liver, Male, Mice, Inbred C57BL, Middle Aged, Plasmids, Oryza, RNA, Messenger, Substrate Specificity, Transfection, RNA, Plant, Computational Biology, Secretory Vesicles, RNA, Untranslated, MicroRNAs, Asian People, Chromatin Immunoprecipitation, Adaptor Proteins, Signal Transducing, Mice, Young Adult, Hep G2 Cells, Herbivory
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