Identification of mistletoe (Viscum album L.) miRNAs and their putative roles in medicinal applications

MicroRNAs (miRNAs) are a class of approximately 22 nucleotides single-stranded non-coding RNA molecules that play crucial roles in gene expression. Zhang et al. suggested that the rice miRNAs might enter mammlian bloodstream and have a functional role in human metabolism [1], which provided thrilling clues that miRNAs might be one of the hidden bioactive compounds in medicinal plants [2].

Viscum album L. (Loranthaceae, European mistletoe) has been widely used for the treatment of cancer and cardiovascular diseases, but its functional compounds have not been well characterized. We assumed that miRNAs might be involved in the pharmacological activities of V. album. In total, 699 conserved miRNAs and 44 novel miRNAs have been identified from V. album. Based on the combination of Targetscan, miRanda, PITA, and RNAhybrid methods, the intersection of 30697 potential human genes have been predicted. These putative human targets were mapped to KEGG database. Interestingly, highly enriched KEGG pathways were associated with some human diseases, especially cancer (e.g. VEGF signaling pathway, transcriptional misregulation in cancer, pathways in cancer and MAPK signaling pathway) and cardiovascular diseases (e.g. VEGF signaling pathway, type II diabetes mellitus, calcium signaling pathway and MAPK signaling pathway), which might explain the clinical use as well as folk medicine use of mistletoe. However, further experimental validation is necessary to confirm these human targets of mistletoe miRNAs. In summary, our study provides indirect evidence for the medicinal use of V. album, more importantly, increases the knowledge regarding the miRNAs mediated cross-kingdom regulation between plants and mammalian.

[1] Zhang et al. Cell Res 2012; 22: 273 – 274

[2] Xie W, Weng A, Melzig M. Planta Med 2016; 82:1153 – 1162