title: Cross-kingdom inhibition of breast cancer growth by plant miR159.
abstract: MicroRNAs (miRNAs) are critical regulators of gene expression, and exert extensive impacts on development, physiology, and disease of eukaryotes. A high degree of parallelism is found in the molecular basis of miRNA biogenesis and action in plants and animals. Recent studies interestingly suggest a potential cross-kingdom action of plant-derived miRNAs, through dietary intake, in regulating mammalian gene expression. Although the source and scope of plant miRNAs detected in mammalian specimens remain controversial, these initial studies inspired us to determine whether plant miRNAs can be detected in Western human sera and whether these plant miRNAs are able to influence gene expression and cellular processes related to human diseases such as cancer. Here we found that Western donor sera contained the plant miRNA miR159, whose abundance in the serum was inversely correlated with breast cancer incidence and progression in patients. In human sera, miR159 was predominantly detected in the extracellular vesicles, and was resistant to sodium periodate oxidation suggesting the plant-originated 2'-O-methylation on the 3' terminal ribose. In breast cancer cells but not non-cancerous mammary epithelial cells, a synthetic mimic of miR159 was capable of inhibiting proliferation by targeting TCF7 that encodes a Wnt signaling transcription factor, leading to a decrease in MYC protein levels. Oral administration of miR159 mimic significantly suppressed the growth of xenograft breast tumors in mice. These results demonstrate for the first time that a plant miRNA can inhibit cancer growth in mammals.
authors.affiliation: Department of Cancer Biology, Duarte, CA 91010, USA.|City of Hope Irell & Manella Graduate School of Biological Sciences, Duarte, CA 91010, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Chin
authors.affiliation: Department of Cancer Biology, Duarte, CA 91010, USA.
authors.forename: Miranda Y
authors.initials: MY
authors.lastname: Fong
authors.affiliation: Department of Medical Oncology, Duarte, CA 91010, USA.
authors.forename: George
authors.initials: G
authors.lastname: Somlo
authors.affiliation: Department of Molecular Medicine, Duarte, CA 91010, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Cores of Synthetic and Biopolymer Chemistry, Duarte, CA 91010, USA.
authors.forename: Piotr
authors.initials: P
authors.lastname: Swiderski
authors.affiliation: Cores of Integrative Genomics, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Cancer Biology, Duarte, CA 91010, USA.
authors.forename: Shizhen Emily
authors.initials: SE
authors.lastname: Wang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000494:pharmacology*; D018749:RNA, Plant / Q000235:genetics* / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D035683:MicroRNAs; D018749:RNA, Plant