Biology Reference
In-Depth Information
Chapter 14
Therapeutic Application of MicroRNAs
in Cancer
Nobuyoshi Kosaka , Fumitaka Takeshita , Yusuke Yoshioka ,
and Takahiro Ochiya
Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene
expression thereby controlling many biological and cellular processes, including
development, organogenesis, and homeostasis. Due to miRNAs ability to target
multiple mRNAs, if miRNA expression is altered, diseases such as cancer can occur
as a consequence of the misregulation of target gene networks. Deregulation of
miRNA expression in cancer cells is caused by a variety of mechanisms such as
genetic alterations, epigenetic regulation, or altered expression of transcription fac-
tors, which target miRNAs. Many recent studies have focused on the development
of novel diagnostic tools and therapeutics in the field of oncology. In this chapter,
we summarize the latest and most significant discoveries for the use of miRNA-
based therapy in various physiological and pathological conditions with particular
focus on cancer. In addition, we discuss a new method for the delivery of miRNA to
a desired site using biologically signi fi cant exosomes.
14.1
Introduction
In 1993, Ambros and colleagues discovered a gene, lin-4, whose product was a
small nonprotein coding RNA, microRNA (miRNA) that affected development in
Caenorhabditis elegans
[
1
]. Currently, there are 1,527 mature human miRNA
sequences listed in the miRNA registry (Sanger miRBase release 18;
http://www.
mirbase.org/
)
. To yield the functional mature miRNA, biogenesis requires several
posttranscriptional processing steps [
2
]. The primary miRNA transcript (pri-
miRNA) is generated in the form of long polycistronic RNA transcripts by RNA
N. Kosaka (
*
) • F. Takeshita • Y. Yoshioka • T. Ochiya
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute,
5-1-1, Tsukiji , Chuo-ku, Tokyo 104-0045 , Japan
e-mail: nkosaka@ncc.go.jp
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