Olea europaea small RNA with functional homology to human miR34a in cross-kingdom interaction of anti-tumoral response

Abstract

Functional foods include compounds with nutritional and health properties. The human diet could play a stronger role in cancer prevention. Only a few studies have described the presence of plant small RNA, in humans who were fed with plant foods, which demonstrated the ability of these molecules to modulate consumer’s genes and evidenced the existence of a plant-animal regulation. Through in silico prediction, Olea europaea small RNAs (sRs), which had been previously reported as miRNAs, were identified, each with functional homology to hsa-miR34a. According to this initial funding, we investigated the ability of oeu-sRs to regulate tumorigenesis in human cells. The transfection of these synthetic oeu-sRs reduced the protein expression of hsa-miR34a mRNA targets, increased apoptosis and decreased proliferation in different tumor cells; by contrast, no effect was observed in PBMCs from healthy donors. The introduction of oeu-small RNA in hsa-miR34a-deficient tumor cells restores its function, whereas cells with normal expression of endogenous hsa-miR34a remained unaffected. The natural oeu-small RNAs that were extracted from O. europaea drupes induce the same effects as synthetic sRs. Careful research on the small RNA sequences executed for mapping and annotation in the genome of O. europaea var. Sylvestris and var. Farga led to the hypothesis that RNA fragments with functional homology to human miRNAs could be generated from the degradation of regions of RNA transcripts. These results indicate the possibility of developing novel natural non-toxic drugs that contain active plant-derived tumor-suppressing small RNA with functional homology to hsa-miRNAs and that can support antineoplastic strategies.

Effect of microvesicles from Moringa oleifera containing miRNA on proliferation and apoptosis in tumor cell lines

“…Following the characterization of the miRs content in MOES MVs, a bioinformatic analysis was performed to identify the possible human genes targeted by the miRs present in the mol-sR pool and involved in the apoptosis mechanism 16,20,35 .…”

“…MiRNAs are short stretches of noncoding RNAs that play an essential role in gene regulation; they regulate protein expression at the post-transcriptional level in animals and plants. More than four hundred conserved miRNAs have been identified from plants, and in silico and in vitro functional validation have highlighted the possible role of plant miRNAs as regulators of protein expression in mammals 11,[14][15][16][17][18][19][20][21] .…”

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

“…Altogether these features might allow a cross-kingdom functional interaction. This hypothesis is supported by a growing number of papers published in the last decade (Minutolo et al, 2018;Li et al, 2018aLi et al, , 2019Link et al, 2019).…”

“…Recently, 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. On the other hand, it has long been known that ingested RNA from food sources in nematodes and insects can control their gene expression (Whangbo and Hunter, 2008).…”

“…More recently, Minutolo et al demonstrated that the natural oeu-sRNAs decrease the protein expression of hsa-miR34a mRNA targets, reducing proliferation and increasing apoptosis in different tumor cells. These miRNAs were extracted from Olea europaea drupes and had been previously reported to have functional homology to hsa-miR34a (Minutolo et al, 2018).…”