Plant miR171 modulates mTOR pathway in HEK293 cells by targeting GNA12

Abstract: Plant microRNAs have shown the capacity to regulate mammalian systems. The potential bioactivity of miR171vr, an isoform of the plant miR171, on human embryonic kidney 293 (HEK293) cells was investigated. Bioinformatics simulations revealed that human G protein subunit alpha 12 (GNA12) transcript could represent an excellent target for miR171vr. To confirm this prediction, in vitro experiments were performed using a synthetic microRNA designed on miR171vr sequence. MiR-treated cells showed a significant decrease of GNA12 mRNA and protein levels, confirming the putative cross-kingdom interaction. In addition, miR171vr determined the modulation of GNA12 downstream signaling factors, including mTOR, as expected. Finally, the effect of the plant miRNA on HEK293 cell growth and its stability in presence of several stressors, such as those miming digestive processes and procedures for preparing food, were evaluated. All this preliminary evidence would suggest that miR171vr, introduced by diet or as supplement in gene therapies, could potentially influence human gene expression, especially for treating disorders where GNA12 is over-expressed (i.e. oral cancer, breast and prostate adenocarcinoma) or mTOR kinase is down-regulated (e.g. obesity, type 2 diabetes, neurodegeneration). Graphic abstract: [Figure not available: see fulltext.].