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Cross-kingdom inhibition of breast cancer growth by plant miR159 FREE

机译：植物miR159 FREE跨界抑制乳腺癌生长

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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.
机译：微小RNA（miRNA）是基因表达的关键调节因子，对真核生物的发育，生理和疾病产生广泛的影响。在miRNA生物发生的分子基础和动植物中的作用中发现了高度的平行性。有趣的是，最近的研究表明，通过饮食摄入植物源性miRNA在调节哺乳动物基因表达中可能具有潜在的交叉作用。尽管在哺乳动物标本中检测到的植物miRNA的来源和范围仍然存在争议，但这些初步研究启发了我们确定是否可以在西方人血清中检测到植物miRNA，以及这些植物miRNA是否能够影响与人类疾病相关的基因表达和细胞过程例如癌症。在这里，我们发现西方供体血清中含有植物miRNA miR159，其血清中的丰度与患者的乳腺癌发生率和进展呈负相关。在人血清中，miR159主要在细胞外囊泡中检测到，并且对高碘酸钠氧化具有抗性，表明植物起源的3'末端核糖上的2'-O-甲基化。在乳腺癌细胞而非非癌性乳腺上皮细胞中，miR159的合成模拟物能够通过靶向编码Wnt信号转录因子的TCF7抑制增殖，从而导致MYC蛋白水平降低。口服miR159模拟物可显着抑制小鼠异种移植乳腺肿瘤的生长。这些结果首次证明了植物miRNA可以抑制哺乳动物中的癌症生长。

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