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2017 ; 135
(ä): 53-118
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Animal Models to Study MicroRNA Function
#MMPMID28882225
Pal AS
; Kasinski AL
Adv Cancer Res
2017[]; 135
(ä): 53-118
PMID28882225
show ga
The discovery of the microRNAs, lin-4 and let-7 as critical mediators of normal
development in Caenorhabditis elegans and their conservation throughout evolution
has spearheaded research toward identifying novel roles of microRNAs in other
cellular processes. To accurately elucidate these fundamental functions,
especially in the context of an intact organism, various microRNA transgenic
models have been generated and evaluated. Transgenic C. elegans (worms),
Drosophila melanogaster (flies), Danio rerio (zebrafish), and Mus musculus
(mouse) have contributed immensely toward uncovering the roles of multiple
microRNAs in cellular processes such as proliferation, differentiation, and
apoptosis, pathways that are severely altered in human diseases such as cancer.
The simple model organisms, C. elegans, D. melanogaster, and D. rerio, do not
develop cancers but have proved to be convenient systesm in microRNA research,
especially in characterizing the microRNA biogenesis machinery which is often
dysregulated during human tumorigenesis. The microRNA-dependent events delineated
via these simple in vivo systems have been further verified in vitro, and in more
complex models of cancers, such as M. musculus. The focus of this review is to
provide an overview of the important contributions made in the microRNA field
using model organisms. The simple model systems provided the basis for the
importance of microRNAs in normal cellular physiology, while the more complex
animal systems provided evidence for the role of microRNAs dysregulation in
cancers. Highlights include an overview of the various strategies used to
generate transgenic organisms and a review of the use of transgenic mice for
evaluating preclinical efficacy of microRNA-based cancer therapeutics.
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