About miRNAs
Small non-coding RNAs known as microRNAs (miRNAs) are promising candidates as therapeutic
and diagnostic agents for many different diseases including cancer. As their name
implies, miRNAs are small RNA molecules, measuring between 17 to 22 nucleotides.
There are more than 800 miRNA-encoding genes in humans. The small, functional RNAs
are highly conserved in vertebrates and comprise approximately 2% of all genes.
miRNAs act as natural antisense molecules by negatively regulating the expression
of genes with sequences that are complementary to the miRNAs. Cell culture and animal
model studies have revealed that the mis-regulation of some miRNAs can contribute
to the development of human malignancies, suggesting that miRNAs can function as
bona fide oncogenes or tumor suppressors. miRNAs regulate the expression of a variety
of genes including many oncogenes, tumor suppressors, and regulators of development
and differentiation. Each miRNA appears to regulate the expression of tens to hundreds
of different genes. In many cases, it appears that miRNA regulate the expression
of multiple, functionally related genes, making it possible to efficiently regulate
the activities of specific cell processes.
Figure 1: Current model of the microRNA mechanism
Figure 2: Peer-reviewed microRNA publications
The ability to affect the expression of multiple genes makes miRNAs an exciting
new candidate for biomarker and drug discovery and development. Disease states,
such as cancer, frequently arise from the altered expression of multiple genes through
several developmental phases. Publications from the laboratories of Harvard Medical
School (Golub) and Ohio State University (Croce) reveal that miRNA expression appears
to be significantly and consistently altered in cancer samples (Lu 2005, Volinia
2006). Yanaihara et al (2006) examined miRNA expression in a series of lung cancer
samples to identify links between miRNAs and lung carcinogenesis. They found that
miRNAs discriminate lung cancers from non-cancerous lung tissues and the expression
of several miRNAs correlate with patient survival. These studies suggest that altered
expression of specific miRNAs might be essential for cancer diagnostic applications
and that miRNAs might represent key intervention points for cancer therapy. Consistent
with this concept, a collaboration between scientists at Asuragen and Yale showed
that a miRNA that is commonly down-regulated in lung tumors regulates the expression
of the key cancer gene, RAS, and that altered expression of let-7 might contribute
to the development of lung cancer (Johnson 2005).
In addition to miRNA expression studies, Asuragen scientists and other researchers
have noted a number of striking relationships between miRNAs and cancer, including:
- When introduced or inhibited in cells, miRNAs can profoundly affect
cancer-related cellular processes
- The expression of genes that are known to be important for cancer
progression are regulated by specific miRNAs
- miRNAs that affect cancer-related cell processes and genes are
often mis-regulated in tumors, suggesting that they contribute to the disease
- miRNAs frequently map to breakpoints in chromosomes that tumor
associated breakpoints
- Over-expressing specific miRNAs in animal models has been shown
to increase the incidence of cancer
- Over-expressing other miRNAs in animal models has been shown to
lead to tumor regression
The prevailing belief in the research community is that some miRNAs act as oncogenes
and others as tumor suppressors, making these small RNAs compelling targets for
cancer therapeutic development as well as being therapeutic entities themselves.
Asuragen holds early patent applications that identify specific miRNAs as therapeutic
targets for cancer and other diseases.
Delivering on the Promise of microRNA Therapeutics -
Mirna Therapeutics, Inc.