Is it possible to obtain a tumor suppressor resistant population from stable transfection with a tumor suppressor miRNA? If the miRNA is supposed to slow proliferation and induce apoptosis, then the only cells remaining from the transfection are supposed to resist these miRNA effects and express the miRNA.
I've asked this question myself many times. I don't remember having seen any work describing this per se. However, I think it's possible: let's think on a tumor suppressor miR that targets a key gene for cell cycle progression. Now, if among your cells there's someone with a mutation in the seed complimentary site in the target gene, that is maybe a cell that will evade the tumor suppressor effect of the miR.
The landscape can be more complicated because most of the miRs target many key genes, sometimes with redundant functions, but I still think it worths a try.
Similar phenomenon has been observed in Tourette syndrome as described by Martin. Here, mutation in the 3'UTR of SLITRK1 gene was found which is a binding site of hsa-mir-189.
http://medicine.yale.edu/labs/sestan/www/Publications/abelsonS05.pdf
It's possible but there may be a problem. One miRNA could suppress multiple genes at the same time so after a period of time the phenotype may disappear in the stable line due to other phenomena start showing up. You only see "miRNA effect(s)" in certain time window.
I was just wondering about the target(s) of miRNAs, especially in tumor cells. The contention that each miRNA can bind to hundreds of target genes at the 3' UTR is based on prediction models, using various algorithms. I would like to know if it has been shown that any one miRNA can in fact bind to many putative targets. Another related question is whether there is evidence for targeting various genes at specific stages of cell cycle by the same miRNA.
- Badges
- Science topic
- Similar topics
- Biological Science
- Molecular Biology
- Biomolecules
- Nucleic Acids
- RNA