Liu Juncheng, Wang Fang, Weng Zebin, Sui Xiaonan, Fang Yong, Tang Xiaozhi, Shen Xinchun
College of Food Science and Engineering, Collaborative Innovation Center for Modern Grain Circulation and Safety, Key Laboratory of Grains and Oils Quality Control and Processing, Nanjing University of Finance and Economics, Nanjing 210046, China.
Basic Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Genomics. 2020 Sep;112(5):2949-2958. doi: 10.1016/j.ygeno.2020.05.011. Epub 2020 May 11.
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.
微小RNA(miRNA)是真核生物中基因表达的重要调节因子。研究表明,植物源miRNA可通过饮食被吸收并调节哺乳动物的基因表达。虽然已有大豆源miRNA的报道,但其生物学功能仍不清楚。在本研究中,我们发现大豆源小RNA(sRNA)显著抑制Caco-2细胞的增殖并促进其凋亡。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,通过预测我们获得了8个与结肠癌相关的靶基因,包括转录因子7(TCF7)。进一步研究表明,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,但在培养的正常黏膜细胞中未上调。这些发现为大豆源miRNA在肿瘤预防中的潜在应用提供了一种新的分子机制。