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.
Highlights
Total RNA was depleted from ribosomal RNA, and directional RNA sequencing produced an average of 17.5 million reads per sample, out of which 60% were aligned to the reference genome
Numerous scientific studies have demonstrated the presence of plant miRNAs in body fluids: serum, saliva, urine, and in gastric and colon mucosa (Minutolo et al, 2018; Li et al, 2019; Link et al, 2019) and demonstrated that these circulating miRNAs might have a significant involvement in miRNA-mediated gene expression regulation
Chin et al (2016) demonstrated that plant miR159 can be identified in human sera and can affect cancer far from the gastrointestinal tract, such as breast cancer, and that its level is inversely associated with breast cancer progression and incidence
Summary
Mature miRNAs are a category of ubiquitous small noncoding RNAs, 16–24 nucleotides long, and evolutionarily conserved (Zhang et al, 2006). These small molecules play significant roles in the modulation of several physiopathological cellular processes such as organism development, cancer, and cancer progression. In plants and animals, mature miRNAs linked to AGO proteins target complementary messenger RNA (mRNA) sequences leading to downregulation or completely inhibition of their expression (Bartel, 2004; LopezGomollon et al, 2012). The main element for AGO protein binding to its mRNA target is a sequence of six to eight nucleotides (seed region), located at the 5 end of the miRNA, sometimes interrupted by a specific G-bulge. An accurate study demonstrated that miRNAs at first suppress mRNA translation and later induce mRNA degradation (Zhang K. et al, 2018)
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