The discovery that noncoding regions of the genome such as microRNAs (miRNAs) can influence the pathogenesis of cancer has led investigators to consider using these molecules to guide clinical decision making. In a symposium this morning, miRNAs in Practice: Little Molecules With A Lot of Punch, Muller Fabbri, MD, PhD, and Vincent De Guire, PhD, will discuss new research on the biology of miRNAs and explore their potential clinical applications.

miRNAs are endogenous, small RNAs that  inhibit gene function by targeting mRNA for either degradation or inhibition of translation. After transcription, they undergo a series of processing steps that culminate in a small, 22-nucleotide RNA that binds to target mRNAs with imperfect complementarity. miRNAs can bind to multiple targets, precipitating global changes in expression patterns. Consequently, aberrant expression of miRNAs can contribute to the pathogenesis of many human diseases.

There are many potential uses for miRNAs in medicine. For example, global alterations in miRNA expression have been described in a large number of malignancies, giving rise to the idea that miRNAs can serve as biomarkers for detection of cancer and prognostics to define therapeutic response. Hundreds of studies have found circulating miRNAs in biological fluids such as blood, urine, and many others.

De Guire will discuss different applications for the use of these small RNAs in diagnostics and therapeutics. He will also discuss preanalytical and analytical variables that influence measurement of circulating miRNAs. Reliable measurement of these molecules can be challenging due to the lack of standardization of variables such as collection, processing, and storage of specimens.

Fabbri will explain how profiles of miRNA expression may differentiate normal versus disease tissue. Small molecule miRNAs are highly stable, abundant, and specific for certain cell types, and research has shown that amounts correlate with several diseases. Fabbri will discuss recent findings showing that dysregulated miRNAs are secreted from tumor cells in small vesicles called exosomes. Intriguingly, Fabbri’s research has shown that surrounding immune cells can engulf these vesicles, and the resulting activation is thought to trigger an inflammatory response that promotes cancer cell growth. These changes in expression of tumor-expressed miRNAs can alter the surrounding tumor microenvironment, raising the possibility that a relationship between a primary tumor and circulating miRNAs may serve as useful noninvasive biomarkers for some cancers.

Because miRNAs can regulate entire pathways rather than single targets, their use as therapeutic agents would have a key advantage over currently available selective protein inhibitors that target only one piece of a pathway and are prone to acquired resistance. If miRNAs can be harnessed in this way as tumor suppressors, they will be an appealing target for developing new therapeutics. 
At the same time, there are several technical challenges to overcome before miRNAs fulfill their promise, such as finding a non-toxic delivery system and concerns about off-target effects. Ultimately, a better understanding of the contribution of miRNAs to complex biological networks is critical before miRNAs can be applied to clinical therapeutics.

“This field is still in relative infancy,” according to the moderator of today’s session, Tina Lockwood, PhD.  “Although several challenges remain, miRNAs undoubtedly have enormous potential to provide diagnostic, prognostic, and theranostic information in human disease.”

Indeed, if miRNAs continue to show promise as biomarkers, they will be very welcome additions to today’s era of personalized medicine.