Plant miRNAs Reduce Cancer Cell Proliferation by Targeting MALAT1 and NEAT1: A Beneficial Cross-Kingdom Interaction

Flaviana Marzano; Mariano Francesco Caratozzolo; Arianna Consiglio; Flavio Licciulli; Sabino Liuni; Elisabetta Sbisà; Domenica D'Elia; Apollonia Tullo; Domenico Catalano

doi:10.3389/fgene.2020.552490

Plant miRNAs Reduce Cancer Cell Proliferation by Targeting MALAT1 and NEAT1: A Beneficial Cross-Kingdom Interaction

Front Genet. 2020 Sep 18:11:552490. doi: 10.3389/fgene.2020.552490. eCollection 2020.

Authors

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

Affiliations

¹ Department of Biomedical Sciences, Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, Bari, Italy.
² Department of Biomedical Sciences, Institute for Biomedical Technologies, Bari, Italy.

Abstract

MicroRNAs (miRNAs) are ubiquitous regulators of gene expression, evolutionarily conserved in plants and mammals. In recent years, although a growing number of papers debate the role of plant miRNAs on human gene expression, the molecular mechanisms through which this effect is achieved are still not completely elucidated. Some evidence suggest that this interaction might be sequence specific, and in this work, we investigated this possibility by transcriptomic and bioinformatics approaches. Plant and human miRNA sequences from primary databases were collected and compared for their similarities (global or local alignments). Out of 2,588 human miRNAs, 1,606 showed a perfect match of their seed sequence with the 5' end of 3,172 plant miRNAs. Further selections were applied based on the role of the human target genes or of the miRNA in cell cycle regulation (as an oncogene, tumor suppressor, or a biomarker for prognosis, or diagnosis in cancer). Based on these criteria, 20 human miRNAs were selected as potential functional analogous of 7 plant miRNAs, which were in turn transfected in different cell lines to evaluate their effect on cell proliferation. A significant decrease was observed in colorectal carcinoma HCT116 cell line. RNA-Seq demonstrated that 446 genes were differentially expressed 72 h after transfection. Noteworthy, we demonstrated that the plant mtr-miR-5754 and gma-miR4995 directly target the tumor-associated long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and nuclear paraspeckle assembly transcript 1 (NEAT1) in a sequence-specific manner. In conclusion, according to other recent discoveries, our study strengthens and expands the hypothesis that plant miRNAs can have a regulatory effect in mammals by targeting both protein-coding and non-coding RNA, thus suggesting new biotechnological applications.

Keywords: MALAT1; NEAT1; cancer; long non-coding; nutrition; plant miRNA.