A novel chemopreventive strategy based on therapeutic microRNAs produced in plants

Mlotshwa, Sizolwenkosi; Pruss, Gail J.; MacArthur, John L.; Endres, Matthew W.; Davis, Celestia; Hofseth, Lorne J.; Peña, Maria Marjorette O.; Vance, Vicki

doi:10.1038/cr.2015.25

Cited by 107 publications

(105 citation statements)

References 11 publications

(12 reference statements)

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“…81,126,127 The plant mimic miRNAs resulted in a massive reduction of tumor progression, moreover, this study has also provided evidence for the active uptake of plant-structured miRNAs in mammals. 78,122 These findings could be even more intriguing by considering the fact that more than half of the world's population consumes plants as primarily nutrients and one-sixth of them suffer from gastrointestinal or chronic kidney diseases that might further affect the absorption and distribution of miRNA. 128 Biotechnologically engineered plants producing miRNAs able to recognize human gene sequences might thus represent a novel direction in therapy, but a very intensive experimental and biotechnological work-up will be needed for this to be realized.…”

Section: Treatment Potential For Xeno-mirnasmentioning

confidence: 99%

“…miR-2911 and its synthetic variant have been shown to accumulate in the lung of mice via microvesicles, suggesting that miR-2911 can be absorbed and encapsulated in microvesicles by intestinal epithelial cells. 124,125 In another very recent study, 122 3 known tumor suppressor miRNAs (miR-34a, miR-143 and miR-145) acting as tumor suppressor in colon cancer, and biotechnologically engineered to be methylated in a plant miRNA fashion have been investigated. 81,126,127 The plant mimic miRNAs resulted in a massive reduction of tumor progression, moreover, this study has also provided evidence for the active uptake of plant-structured miRNAs in mammals.…”

Section: Treatment Potential For Xeno-mirnasmentioning

confidence: 99%

“…121,122 A recent study revealed that the long-known beneficial effect of honeysuckle decoction (Lonicera japonica) traditionally used in Chinese medicine against flu might imply miRNA. A rRNA-derivedatypical miRNA, miR-2911 has been identified that is resistant to boiling and can reach an adequate amount in the honeysuckle decoction.…”

Section: Treatment Potential For Xeno-mirnasmentioning

confidence: 99%

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Potential relevance of microRNAs in inter-species epigenetic communication, and implications for disease pathogenesis

et al. 2016

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MicroRNAs are short non-protein coding RNA molecules involved in the epigenetic regulation of gene expression. Recently, extracellular microRNAs have been described in body fluids that might enable epigenetic communication between distant tissues. Being highly conserved molecules, exogenous xenomicroRNAs from different species could affect gene expression in the host even in a cross-kingdom fashion. Several data underline the relevance of microRNA-mediated communication between virus and host, and there are some experimental data showing that plant-or animal-derived dietary microRNAs might have gene expression modulating activity in humans. Milk-derived microRNAs might be involved in the "epigenetic priming" of the baby. Exogenous microRNAs might be hypothesized to be implicated in disease pathogenesis, e.g. in tumors. Major questions remain to be addressed including the amount of xeno-microRNAs needed for biological action or routes for microRNA delivery. In this brief review, experimental data and hypotheses on the potential pathogenic inter-species relevance of microRNA are presented.Abbreviations: AGO2, Argonaute-2 protein; dsRNA, double stranded RNA; FoxO1, forkhead box class O1A; FOXP3, forkhead box P3; HDL, high density lipoprotein; LDL, low density lipoprotein; LDLRAP1, low-density lipoprotein receptor adapter protein 1; miRNA, miR, microRNA; mTORC1, mechanistic target of rapamycin complex 1; premiRNA, precursor microRNA; pri-miRNA, primary microRNA; RISC, RNA-induced silencing complex; RUNX2, runt related transcription factor 2; siRNA, small interfering RNA; TCF7, transcription factor 7; TLR, Toll-like receptor; Treg, regulatory T-cell; ZEB1, zinc finger E-box binding homeobox 1

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Section: Treatment Potential For Xeno-mirnasmentioning

confidence: 99%

Section: Treatment Potential For Xeno-mirnasmentioning

confidence: 99%

Section: Treatment Potential For Xeno-mirnasmentioning

confidence: 99%

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Potential relevance of microRNAs in inter-species epigenetic communication, and implications for disease pathogenesis

et al. 2016

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“…However, in the meantime, enthusiasm about the absorption and function of xenomiRs has been diminished by negative findings and evidence of contamination and experimental design flaws that account for apparently positive results (Mlotshwa et al 2015).…”

Section: Kenneth W Witwer Johns Hopkins University School Of Medicimentioning

confidence: 99%

Advancing the use of noncoding RNA in regulatory toxicology: Report of an ECETOC workshop

Aigner¹,

Buesen²,

Gant³

et al. 2016

Regulatory Toxicology and Pharmacology

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The European Centre for the Ecotoxicology and Toxicology of Chemicals (ECETOC) organised a workshop to discuss the state-of-the-art research on noncoding RNAs (ncRNAs) as biomarkers in regulatory toxicology and as analytical and therapeutic agents. There was agreement that the abundance of data obtained from ncRNA expression profiling requires careful evaluation to determine the utility of specific ncRNAs for regulatory toxicology. To advance the use of ncRNA in regulatory toxicology, the following research priorities were identified: (1) Conduct comprehensive literature reviews to identify candidate ncRNAs for further assessment as potential biomarkers of toxicity and areas of toxicology where ncRNA expression profiling can address prevailing scientific deficiencies.(2) Develop consensus on how to conduct and report ncRNA expression profiling in a toxicological context to support applicability for regulatory decision-making. (3) Conduct experimental projects to evaluate the toxicological relevance of the expression profiles of selected ncRNAs. As necessary, retrospective analyses (e.g. from surplus samples from control groups from regulatory studies) can be supplemented with new (90-day) rat oral toxicity studies. These projects should aim at establishing physiological ncRNA expression profiles including the biological variability of healthy individuals. To substantiate the relevance of key ncRNAs for cell homeostasis or pathogenesis, molecular events should be linked with substance-induced apical effects in a dose-dependent manner. Applying a holistic approach, knowledge on ncRNAs, and relevant information from 'omics and epigenetics technologies, should be integrated into adverse outcome pathways to improve the understanding of the functional roles of ncRNAs within a regulatory context.

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“…More recently, it has been suggested that dietary uptake could be enhanced via intestinal or renal injury, but only with artificially high levels of oral ingestion. 28,29 In total, such work may suggest that horizontal miRNA transfer is possible, but severely limited under naturally occurring conditions in multiple organisms, including mice, humans, and honey bees. Nonetheless, controversy remains.…”

Section: Introductionmentioning

confidence: 99%

Negligible uptake and transfer of diet-derived pollen microRNAs in adult honey bees

et al. 2015

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The putative transfer and gene regulatory activities of diet-derived miRNAs in ingesting animals are still debated. Importantly, no study to date has fully examined the role of dietary uptake of miRNA in the honey bee, a critical pollinator in both agricultural and natural ecosystems. After controlled pollen feeding experiments in adult honey bees, we observed that midguts demonstrated robust increases in plant miRNAs after pollen ingestion. However, we found no evidence of biologically relevant delivery of these molecules to proximal or distal tissues of recipient honey bees. Our results, therefore, support the premise that pollen miRNAs ingested as part of a typical diet are not robustly transferred across barrier epithelia of adult honey bees under normal conditions. Key future questions include whether other small RNA species in honey bee diets behave similarly and whether more specialized and specific delivery mechanisms exist for more efficient transport, particularly in the context of stressed barrier epithelia.

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A novel chemopreventive strategy based on therapeutic microRNAs produced in plants

Cited by 107 publications

References 11 publications

Potential relevance of microRNAs in inter-species epigenetic communication, and implications for disease pathogenesis

Potential relevance of microRNAs in inter-species epigenetic communication, and implications for disease pathogenesis

Advancing the use of noncoding RNA in regulatory toxicology: Report of an ECETOC workshop

Negligible uptake and transfer of diet-derived pollen microRNAs in adult honey bees

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