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Table 1 Supporting evidence of cross-kingdom communication by diet/plant-derived miRNAs

From: MicroRNAs from plants to animals, do they define a new messenger for communication?

Year Contents miRNAs involved Source origin miRNA levels Potential mechanism Function Detection methods Conclusion Reference
2012 Plant miRNAs were present in human and animal sera and organs. miR168a Rice fM Level Associated with AGO2 complex and
packaged in MVs
miR168a regulated mouse LDLRAP1 expression and consequently decreased LDL removal from mouse plasma. HTS, RT-qPCR, Bioinformatics, NB, WB, AGO2 immunoprecipitation Exogenous plant miRNAs in food could regulate the expression of target genes in mammals. [28]
2014 miR172 from cabbage (Brassica oleracea) was detected in blood, spleen, liver and kidney of mice after feeding with plant extract. miR172 Cabbage Stomach contained about 4.5–0.4% (2–24 h after feeding), intestines 2.4–0.2% (2–36 h), blood 1.3–0.2% (2–72 h) and spleen 0.38–0.04% (2–72 h) of the miR172 orally administered. sRNA could survive for more than 36 h in blood and fecal samples No phenotypic changes were found in all the mice fed with the foreign RNA. RT-qPCR,
Electrophoresis
Exogenous plant miRNAs could survive in the murine GI tract, enter peripheral blood and continue to access other organs. [142]
2015 Plant miRNAs were detectable in human plasma of volunteers after drinking juice. 18 plant miRNAs (miR156a, miR157a, miR158a, etc.) Watermelon juice and mixed fruits fM Level largely encapsulated in MVs Not mentioned RT-qPCR,
NB
Plant miRNAs in human plasma could be efficiently detected and reliably compared by RT-qPCR. Provided a SOP for measuring plant miRNAs in human and animal plasma. [143]
2015 Even after an extensive pretreatment, plant-derived miRNA delivered by typical dietary ingestion remained bioavailable for uptake during early digestion. miR166, miR167, miR168 Soybean and rice In vitro methods Not mentioned Not mentioned RT-qPCR Storage, processing and cooking did not abolish plant miRNAs in food. [149]
2014 miR2911 was highly stable in honeysuckle decoction, and continuous drinking or gavage feeding of honeysuckle decoction significantly elevated miR2911 levels in mouse blood and lung. miR2911 Honeysuckle fM Level A unique sequence and high GC content, MVs-mediated pathway miR2911 could directly target multiple viral genes and suppress viral infections. HTS, RT-qPCR, NB, Fluorescent labeled tracing assay, Luciferase reporter assay, Ago2 immunoprecipitation Provided evidence of physiological function of exogenous plant miRNAs in human and animals. [29]
2015 Using a chow diet containing honeysuckle, plant-based sRNAs could be detected in sera and urine of mice miR2911, miR168a Honeysuckle fM Level Consumers of particular diets and/or with increased intestinal per- meability Altered or damaged guts lining could enhance dietary miRNA uptake. RT-qPCR, droplet digital PCR Dietary sRNAs could survive circulation and are excreted in urine. [144]
2015 miR2911 was detectable in sera and urine of the honeysuckle decoction-consuming mice. miR2911 Dried herbs or flowers fM Level Circulating miR2911 was not bound by AGO2, but due to high GC content. Not mentioned RT-qPCR,
AGO2 immunoprecipit-ation
The uptake of miR2911 might be a more commonplace phenomenon that could occur when eating a variety of plant-based foods. [145]
2016 Plant-based miR2911 was measured 7 days after feeding in animals. miR2911 Plants fM Level Circulating miR2911 was not associated with exosomes, but possibly with a protein. Not mentioned RT-qPCR Mice consuming diets rich in vegetables displayed enhanced serum levels of plant specific miR2911. [146]
2017 Plant-derived miR2911 was detectable in sera of mice fed with various vegetables. miR2911 Cabbage
Arabidopsis
miR2911 was detectable while other plant-based miRNAs failed to detect. Increased levels of miR2911 correlated with the degradation of plant foods and rRNAs. Not mentioned RT-qPCR, Bioinformatic, Dual-luciferase reporter assay, Provided insights into the atypical bioavailability of miR2911 and offered engineering strategies for plant-based sRNA therapeutics. [147]
2015 Orally administered tumor suppressor miRNAs reduced tumor burden in ApcMin/+ mice and were detectable in intestinal tissue. miR34a, miR143, miR145 Synthesized methylated miRNAs Intestinal miR34a was at a detectable level; detection of miR143 and miR145 in mouse intestines were failed. Not mentioned Reduced tumor burden in the well-established ApcMin/+ mouse model of colon cancer. RT-qPCR,
Dissecting microscope.
Tumor suppressor miRNAs designed to mimic sRNAs produced in plants were taken up by the digestive tract of ApcMin/+ mice upon ingestion. [150]
2016 Plant miR159 could be detected in human sera and tumor tissues, and was associated with breast cancer progression. miR159 Synthesized methylated miRNAs fM Level Predominantly present in MVs The miR159 in human serum was capable of inhibiting cell proliferation. RT-qPCR, HTS, Dual-luciferase reporter assay, In situ hybridization, Immunohistochemistry, WB The feasibility of using synthetic forms of plant miRNAs as dietary supplements in the treatment of human cancers, including those outside of the GI track. [151]
2016 Strawberry fruit FvmiR168 affected properties of dendritic cells and their ability to respond to inflammatory stimuli. FvmiR168 Strawberry fruit biologically relevant amount The immune-modulatory effect of plant miRNA was not sequence or plant specific. Plant-based miRNAs modified dendritic cells ability to respond to inflammatory agents by limiting T cell proliferation. RT-qPCR, Flow cytometry, Fluorescence microscopy A potential for therapeutic use of plant miRNAs in the prevention of chronic inflammation related diseases. [152]
2017 Ingestion of wild type blood increased the levels of miR451 and miR144 in peripheral blood of miR144/451-null mice miR451
miR144
Wild type mice blood At very low level but biologically relevant amount Exosomes Exogenous miR451 existing in miR144/451 knockout mice enhanced anti-oxidant activity in vivo via increasing the activity of Foxo3 pathway Two different RT-qPCR, Dual-luciferase reporter assay, WB, FACS miRNAs in foods or dietary supplements could affect the functions of the consumer. [153]
  1. MVs microvesicles, HTS high-throughput sequencing; RT-qPCR quantitative real time polymerase chain reaction, NB Northern blot, WB Western blot, ELISA enzyme-linked immunosorbent assay, FACS Fluorescent activated cell sorting, SOP standard operating procedure, rRNAs ribosomal RNAs, fM femtomole (10−12 mol/L)