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Plant micro RNAs can control cancer genes expression through a sequence-specific targeting mechanism: the case of MALAT1 and NEAT1

Flaviana Marzano1, Mariano Francesco Caratozzolo1, Arianna Consiglio2, Flavio Licciulli2, Sabino Liuni2, Elisabetta Sbisà2, Domenica D’Elia2✉, Apollonia Tullo1, Domenico Catalano2

1 Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, National Research Council, Bari, Italy

2 Institute for Biomedical Technologies, National Research Council, Bari, Italy

Competing interests: FM none; MFC none; AC none; FL none; SL none; ES none; DD none; AT none; DC none

It is well known that some plant compounds, or phytochemicals, can positively affect human health by reducing inflammation and oxidative stress (Issa et al., 2006; Dell’Agli et al., 2013). Although the large number of works published, the molecular mechanisms through which plants can impact human health are still unclear. Recent studies suggest that plant nutrients control the expression of human genes by DNA methylation and histone modifications (Choi and Friso, 2010; Tollefsbol 2014). Moreover, some plant/food-derived microRNAs (miRNAs) accumulate in the sera and tissues of various animals and regulate their gene expression in a sequence-specific manner (Zhang et al., 2012; García-Segura et al., 2013).

We performed a study using a combined in silico and experimental approach to investigate the potential effects and elucidate the molecular mechanisms of edible plant miRNAs on the expression of human genes involved in cancer onset and progression (Marzano et al., 2020). This study demonstrates that plant miRNAs can bind human transcripts in a sequence-specific manner and that their binding is functional. In particular, we have shown that the plant mtr-miR-5754 and gma-miR-4995 directly target the tumour-associated long non-coding RNAs MALAT1 and NEAT1, respectively, in a sequence-specific manner, thus reducing cancer cell proliferation. For the first time, we provide evidence that plant miRNAs can also target human regulatory ncRNAs. These findings open the way to new biotechnological applications in human nutrition and chronic diseases prevention.

Acknowledgements

This work was supported by the National Research Council (CNR) MIUR Flagship Project InterOmics.

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