Uptake and Function Studies of Maternal Milk-derived MicroRNAs

Title, Alexandra C.; Denzler, Rémy; Stoffel, Markus

doi:10.1074/jbc.m115.676734

Cited by 143 publications

(123 citation statements)

References 41 publications

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“…99,100 Transgenic mouse studies found no uptake of specific milk microRNAs. 101,102 Finally, positive results from a milk intake study involving humans 103 could not be validated. 104 Exciting and new concepts in the microRNA oeuvre must be supported by rigorous data.…”

Section: Case Studies To Identify Rigor and Reproducibility Challengementioning

confidence: 99%

Toward the promise of microRNAs – Enhancing reproducibility and rigor in microRNA research

2016

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The fields of applied and translational microRNA research have exploded in recent years as microRNAs have been implicated across a spectrum of diseases. MicroRNA biomarkers, microRNA therapeutics, microRNA regulation of cellular physiology and even xenomiRs have stimulated great interest, which have brought many researchers into the field. Despite many successes in determining general mechanisms of microRNA generation and function, the application of microRNAs in translational areas has not had as much success. It has been a challenge to localize microRNAs to a given cell type within tissues and assay them reliably. At supraphysiologic levels, microRNAs may regulate hosts of genes that are not the physiologic biochemical targets. Thus the applied and translational microRNA literature is filled with pitfalls and claims that are neither scientifically rigorous nor reproducible. This review is focused on increasing awareness of the challenges of working with microRNAs in translational research and recommends better practices in this area of discovery.

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Section: Case Studies To Identify Rigor and Reproducibility Challengementioning

confidence: 99%

Toward the promise of microRNAs – Enhancing reproducibility and rigor in microRNA research

2016

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“…It has been suggested that miRNAs can be transferred from breast milk to the bloodstream (Munch et al 2013;Baier et al 2014;Izumi et al 2015), although these results have also been contested (Laubier et al 2015;Title et al 2015).…”

Section: Controlled Feeding In Piglets Does Not Support Transfer Of Mmentioning

confidence: 99%

Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts

Kang

Bang-Berthelsen

Holm

et al. 2017

RNA

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miRNAs are small 22-nucleotide RNAs that can post-transcriptionally regulate gene expression. It has been proposed that dietary plant miRNAs can enter the human bloodstream and regulate host transcripts; however, these findings have been widely disputed. We here conduct the first comprehensive meta-study in the field, surveying the presence and abundances of cross-species miRNAs (xenomiRs) in 824 sequencing data sets from various human tissues and body fluids. We find that xenomiRs are commonly present in tissues (17%) and body fluids (69%); however, the abundances are low, comprising 0.001% of host human miRNA counts. Further, we do not detect a significant enrichment of xenomiRs in sequencing data originating from tissues and body fluids that are exposed to dietary intake (such as liver). Likewise, there is no significant depletion of xenomiRs in tissues and body fluids that are relatively separated from the main bloodstream (such as brain and cerebro-spinal fluids). Interestingly, the majority (81%) of body fluid xenomiRs stem from rodents, which are a rare human dietary contribution but common laboratory animals. Body fluid samples from the same studies tend to group together when clustered by xenomiR compositions, suggesting technical batch effects. Last, we performed carefully designed and controlled animal feeding studies, in which we detected no transfer of plant miRNAs into rat blood, or bovine milk sequences into piglet blood. In summary, our comprehensive computational and experimental results indicate that xenomiRs originate from technical artifacts rather than dietary intake.

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“…42 In the other 2 models, miR-375 and miR-200c/141 knockout mice fed by wild-type wet nurse mice were explored. 42,45 Only a modest increment in the plasma concentration of these 2 miRNAs was noted, and the authors concluded that milk miRNAs serve just as a dietetic source. However, both miR-375 and miR-200c might also affect exosome formation via exocytotic/endocytotic pathways, 42,48,49 and the required amount of miRNAs for biological activity is also intensively debated.…”

Section: Dietary Milk-derived Mirnasmentioning

confidence: 99%

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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Uptake and Function Studies of Maternal Milk-derived MicroRNAs

Cited by 143 publications

References 41 publications

Toward the promise of microRNAs – Enhancing reproducibility and rigor in microRNA research

Toward the promise of microRNAs – Enhancing reproducibility and rigor in microRNA research

Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts

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

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