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Fig. 14.2
Predicted obstacles to the therapeutic application of miRNA. miRNAs are processed by
various types of proteins. If the introduction of plasmid-based delivery or virus-based miRNA vec-
tors is extremely large, an excessive number of pre-miRNAs are produced, that may disrupt the
transportation of endogenous pre-miRNAs from the nucleus to the cytoplasm mediated by
Exportin-5, resulting in the downregulation of endogenous miRNAs (A). In addition, there are
several inhibitory pathways for the processing of pre-miRNAs to mature miRNAs. For instance,
LIN28, which is upregulated in several kinds of human cancer, specifically binds to the precursor
of let-7 and induces its degradation (B). As another example, MCPIP1 binds to many kinds of pre-
miRNAs and is a nuclease itself that degrades multiple miRNAs by directly cleaving the terminal
loop (C). Administration of a miRNA mimic greatly increases the amounts of miRNAs in the cells,
resulting in the competition between the miRNA mimic and the endogenous miRNAs for the intra-
cellular machinery that processes miRNAs, leading to the possibility that endogenous miRNAs
might lose their function (D)
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