Milk-derived exosomes (MDEs) have a different biological effect on normal fetal colon epithelial cells compared to colon tumor cells in a miRNA-dependent manner

牛奶来源的外泌体 (MDE) 以 miRNA 依赖的方式对正常胎儿结肠上皮细胞和结肠肿瘤细胞产生不同的生物学作用

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作者:Shimon Reif, Yaffa Elbaum Shiff, Regina Golan-Gerstl

Background

Breastfeeding is the ideal source of infant nutrition. Human milk consists not only of nutrients but also biologically active components. Among these latter compounds, exosomes contain proteins, lipids, mRNAs and miRNAs.

Conclusions

In conclusion, the positive effect of exosomes on normal cells without affecting tumor cells may presents an aspect of their safety when considering it use as a nutritional supplement to infant formula.

Methods

To elucidate the biological effects of milk-derived exosomes (MDEs) on normal colonic epithelial cells compared to colonic tumor cells, we incubated cells with MDEs. MDEs were able to enter into normal and tumor cells and change their miRNA expression profiles. Proliferation, cell morphology and protein expression were analyzed in these cells.

Results

Human milk-derived exosomes induced proliferation- and epithelial mesenchymal transformation-related changes, such as collagen type I and twist expression, in normal but not in tumor cells. PTEN, a target of miRNA-148a, was downregulated in normal but not in tumor cells following incubation with MDEs. Moreover, miRNA-148a-3p knockdown cells were used to demonstrate the importance of miRNA in the effect of exosomes on cell proliferation and protein expression. MDEs inhibited proliferation and DNMT1 expression in cells with knockdown of miRNA-148a. Conclusions: In

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