Soybean-derived miRNAs specifically inhibit proliferation and stimulate apoptosis of human colonic Caco-2 cancer cells but not normal mucosal cells in culture

Soybean-derived miRNAs specifically inhibit proliferation and stimulate apoptosis of human colonic Caco-2 cancer cells but not normal mucosal cells in culture
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大豆来源的 miRNA 特异性抑制人结肠 Caco-2 癌细胞的增殖并刺激细胞凋亡,但对培养的正常粘膜细胞没有影响

DOI:
10.1016/j.ygeno.2020.05.011
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发表时间:
2020-09-01
期刊:
影响因子:
4.4
通讯作者:
Shen, Xinchun
Shen, Xinchun
中科院分区:
生物学3区
文献类型:
--
作者:
Liu, Juncheng;Wang, Fang;Shen, Xinchun

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MicroRNA (miRNA) 是真核生物基因表达的重要调节因子。研究表明,植物来源的 miRNA 可以通过饮食吸收并调节哺乳动物的基因表达。尽管大豆来源的 miRNA 已有报道,但其生物学功能仍不清楚。在这项研究中,我们发现大豆来源的小RNA (sRNA) 显着抑制Caco-2 细胞的增殖并刺激其凋亡。生物信息学分析表明,大豆miRNA的靶基因集在癌症通路中广泛富集。此外,我们通过预测获得了与结肠癌相关的8个靶基因,其中包括转录因子7(TCF7)。进一步的研究表明,gma-miR159a抑制Caco-2细胞的增殖,并通过抑制TCF7蛋白在sRNA的抑制作用中发挥重要作用,TCF7蛋白在结肠癌细胞中上调,但在培养的正常粘膜细胞中不上调。这些发现为大豆来源的 miRNA 在肿瘤预防方面的潜在应用提供了一种新的分子机制。
MicroRNAs (miRNAs) are important regulators of gene expression in eukaryotes. Studies have shown that plant-derived miRNAs can be absorbed through diets and regulate gene expression in mammals. Although soybean-derived miRNAs have been reported, their biological functions are still unclear. In this study, we found that soybean-derived small RNAs (sRNAs) significantly inhibited the proliferation and stimulated the apoptosis of Caco-2 cells. Bioinformatics analysis indicated that the target gene set of soybean miRNAs was extensively enriched in cancer pathways. Besides, we obtained 8 target genes, including Transcription factor 7 (TCF7), associated with colon cancer through prediction. Further studies showed that gma-miR159a inhibited the proliferation of Caco-2 cells and played an important role in the inhibitory effect of sRNAs by inhibiting TCF7 protein, which are upregulated in colon cancer cells but not normal mucosal cells in culture. These findings provide a novel molecular mechanism of soybean-derived miRNAs for potential application in tumor prevention.