microRNA Biomarkers as Potential Diagnostic Markers for Cancer - Genomic Biomarkers for Pharmaceutical Development - page 92

CHAPTER
5
microRNA Biomarkers as
Potential Diagnostic Markers
for Cancer
Elizabeth Mambo, Anna E. Szafranska-
Schwarzbach, Gary Latham, Alex Adai, Annette
Schlageter, Bernard Andruss
Asuragen, Inc., Austin, Texas
5.1 OVERVIEW OF microRNAs (miRNAs)
5.1.1 Small Non-Coding RNAs Play a Pivotal Role in Translational Control
MicroRNAs (miRNAs) are small (18-25 nucleotide) non-coding RNAs that control pro-
tein expression by binding to complementary sites on target messenger RNA (mRNA)
transcripts, which results in the inhibition of the translation and / or degradation of the tar-
get mRNA [1] . Although miRNAs are present in eukaryotes, they have also been identified
in organisms such as viruses and algae that are, in evolutionary distance, light years away
from humans. This evolutionary conservation would suggest that miRNAs play an indis-
pensable role in cellular functions. Indeed, they have been found to regulate critical cellular
processes, such as apoptosis [2] , cell proliferation [3] , and cell differentiation [4,5] . More than
2000 mature, human miRNAs have been identified ( http: // www.mirbase.org / , release 20, July
2013) [6] . Each miRNA can regulate the expression of multiple genes, and several different
miRNAs can bind to a single mRNA transcript, thereby resulting in profound effects on gene
expression and cellular functions [7,8] . Due to the involvement of miRNAs in critical cellu-
lar functions, they have been implicated in a number of diseases, including cancer, in which
cell proliferation and apoptosis are dysregulated. The expression of some miRNAs has been
shown to be dysregulated in cancer relative to normal tissues [9,10] , giving rise to the idea
that miRNAs can function both as tumor suppressors and oncogenes, and are promising ana-
lytes for diagnosis, prognosis and therapy.