Related Publications:

  • Oncogene

    • MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma


  • PNAS

    • miR-15 and miR-16 induce apoptosis by targeting BCL2


  • Nature

    A microRNA polycistron as a potential human oncogene


  • Cell

    • RAS Is Regulated by the let-7 MicroRNA Family


Welcome to Asuragen Therapeutics


microRNAs as Therapeutics

microRNAs are a Compelling New Class of Cancer Therapeutic Targets

Small non-coding RNAs known as microRNAs (miRNAs) are promising candidates as therapeutic agents for many different diseases including cancer. As their name implies, miRNAs are small RNA molecules, measuring approximately 22 nucleotides. There are more than 500 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. 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 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

Like antisense oligonucleotides, siRNAs, and other oligonucleotide-based drugs, miRNAs do not freely diffuse into cells and thus require assistance to enter disease cells.Therapeutic applications of miRNAs will benefit significantly from the on-going efforts of Novartis, Merck, Alnylam, Sirna, and others who are developing technologies that facilitate the use of siRNAs as therapeutics. Like miRNAs, siRNAs are small RNAs that function in the cytoplasm and affect gene expression. The therapeutic application of both siRNAs and miRNAs will require delivery technologies that enable synthetic versions of the RNAs to be efficiently delivered to disease cells and tissues.


While the physical characteristics of siRNAs and miRNAs are similar, their biologies are very different. An siRNA is designed to bind to and degrade a single messenger RNA, thereby decreasing the overall level of the protein produced by that messenger RNA. In contrast, miRNAs are naturally occurring functional RNAs that regulate the expression of multiple genes to coordinate the development, differentiation, and functions of cells and tissues. Mis-regulation of individual miRNAs can have dire consequences including the development of diseases like cancer. Correcting the levels of a single miRNA by introducing an inhibitor or synthetic mimic of the miRNA into cancer cells can reactivate pathways regulated by the miRNA and lead to the death of the cancer cells. If the early indications that the altered expression of miRNAs is a key step in the development of cancer, then miRNA mimics and inhibitors are likely to prove to be a remarkably important new class of targeted therapeutics for the treatment of cancer.


Asuragen has an active research program in both the diagnostic and therapeutic applications of miRNAs. It has numerous collaborations with both academic and industrial groups. We encourage interested parties to contact us at miRNAcollaborations@asuragen.com.