Mistletoe and cancer: does microRNA play a role?

Mistletoe, a parasitic plant, is commonly used in Europe as a complementary treatment in cancer patients, improving quality of life and possibly prolonging survival. Although there are several mechanisms that may be responsible for its beneficial effects, the relatively recent discovery of microRNA (miRNA) as a biological regulator suggests another possibility.

Mistletoe, as an obligate parasite, depends on its host tree for its reproduction, and, depending on the mistletoe species, either partially or almost entirely dependent for its survival on its host tree remaining healthy enough to supply nutrients. It would make sense, therefore, that mistletoe might have evolved mechanisms to control the health and survival of its host tree.

It is known that parasitic plants such as dodder (Cuscuta campestris) have evolved mechanisms to control their hosts, for example with cross-species microRNA (miRNA) that target host messenger RNA1. It has also been shown that small RNAs (sRNA) including small interfering RNAs (siRNAs) and miRNAs can mediate communication between kingdoms, eg from plants to fungi2 and even to animals3.

If mistletoe were to use these mechanisms to control its host, what specific systems might be affected? One possibility would be the LET-7 family of microRNAs. The lethal-7 (let-7) gene was first discovered in the nematode as a key developmental regulator, and has since been confirmed in a wide range of species.

  1. Shahid S, Kim G, Johnson NR et al. MicroRNAs from the parasitic plant Cuscuta campestris target host messenger RNAs. Nature. 2018;553:82-85. PMID 29300014
  2. Cai Q, Qiao L, Wang M et al. Plants send small RNAs in extracellular vesicles to fungal pathogen to silence virulence genes. Science. 2018;360:1126-1129. PMID 29773668
  3. Zhou G, Zhou Y, Chen X. New Insight into Inter-kingdom Communication: Horizontal Transfer of Mobile Small RNAs. Front Microbiol. 2017;8:768. PMID 28507539
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