miRNA Biomarkers

What are microRNAs?
MicroRNAs (miRNAs) represent a class of small non-coding ribonucleic acids (RNAs) with peculiar functions in control of gene expression at post-transcriptional level (Zamore et al. 2005). The micro-RNAs mature form is a single stranded RNA, averaging 22 nucleotides long, whose maturation steps take place in part in the nucleus and in part in the cytoplasm. MicroRNAs are transcribed from their own genes scattered in all chromosomes in humans.

Figure 1. Biogenesis of the microRNAs 

miRNAs in cancer
Calin et al published the first report describing a link between miRNAs and cancer in 2002. The authors described how a critical genomic region frequently deleted in chronic lymphocytic leukemia (CLL), 13q14, contains two miRNA genes, miR-15a and miR16-1. Further studies confirmed the link between the lack of these two miRNAs and the development of CLL.
Since then a multitude of studies have been reported describing how chromosomal regions containing miRNAs involved in the negative regulation of a transcript encoding for tumor suppressor genes can be amplified in cancer development. The overexpression of these specific miRNAs would cause the tumor suppressor genes to be silenced.
Conversely, miRNAs repressing oncogenes are often located in fragile loci, where deletions or mutations can occur and result in reduced microRNA levels and overexpression of the target oncogene.
Genome-wide profiling shows that miRNA expression signatures (group of miRNA expressed in a specific biological context) allowed different types of cancer to be discriminated with high accuracy and the tissue of origin of poorly differentiated tumors to be identified.  

Circulating miRNAs
Various studies have shown that miRNAs are released by the cells into the extracellular space to function as modulators of the surrounding and distant tissues. miRNAs are released within vesicles (such as exosomes) or complexed with proteins so they are stable in blood. In recent years circulating miRNAs have become attractive candidates to be used as cancer biomarkers.

MicroRNAs key facts

  • short ribonucleic acid (RNA) molecules (average 22 nucleotides)

  • noncoding RNAs that regulate gene expression by binding complementary sequences of target mRNAs and inducing their degradation or translational repression

  • single miRNAs have multiple targets

  • miRNAs remain intact and stable in plasma/serum