Biology Reference
In-Depth Information
Chapter 3
Approaches to the Modulation of miRNA Maturation
Valerie T. Tripp , Jaclyn R. McKenna , and Douglas D. Young
Abstract
The therapeutic importance of microRNA (miRNA) regulation has recently been realized as these small,
noncoding RNAs have been demonstrated to be involved with a plethora of diseases and disorders. Due
to the complex miRNA maturation process, the expression of these important biomolecules can be manip-
ulated at various stages of the pathway. This review examines both in vivo and in vitro mechanisms and
assays that have been developed to regulate miRNA levels. Modulation of miRNA maturation can be
accomplished via several therapeutic agents, including small molecules and oligonucleotides, in both
specifi c and nonspecifi c fashions. Due to the relevance of miRNAs, these novel therapeutic approaches
represent new tools for the treatment of various cancers and other deleterious disorders.
Key words
miRNA maturation, Small-molecule therapeutics, miRNA assays, Antisense agents
1
Introduction
Knowledge about the biological relevance of microRNAs (miRNAs)
has grown exponentially in the past several years, specifi cally their
involvement in gene regulation and disease progression [
1
-
5
].
These small 21-23mer RNA nucleotides were long thought to be
cellular “junk”; however, they have now been demonstrated to
post-transcriptionally modulate gene expression by site-specifi cally
binding mRNA transcript [
6
-
10
]. Over 900 human miRNA genes
have been reported, and it is thought that they regulate over one-
third of all human genes [
11
,
12
]. Their importance has been
demonstrated in cell proliferation, cell differentiation, and various
developmental processes as well as a range of disease states includ-
ing various forms of cancer and viral replication cycles [
13
-
18
].
Typically, misregulation of miRNA levels can be correlated to sev-
eral cancers and other disorders [
19
-
22
]. The restoration (typically
by antisense technologies) of normal miRNA levels has been
demonstrated to correct the disease state, often by induction of
apoptosis of the diseased cells [
23
-
25
]. Consequently, miRNAs
