miRNAs

MicroRNAs (miRNAs) are small, approximately 20-nucleotide-long, non-coding single-stranded RNA molecules regulating the expression of target genes by imperfect (in animals) binding to the 3′-untranslated region (UTR) and possibly 5′-UTR of mRNA.

To become the mature form, miRNAs are processed by enzymatic complexes Dorsha and Dicer, and they repress translation or lead to the degradation of the mRNA of their target genes.

Currently approximately 2000 human miRNA sequences have been identified, and this number continues to grow.

Regardless of the relatively small number of miRNAs, as each single miRNA targets several hundred genes, and a single target gene can bind to multiple miRNAs, thus making the whole network very complex, it is believed that approximately 30% of all human genes are a target for miRNA regulation.

There is also evidence that these small molecules are expressed in a tissue-/cell-specific manner, being reserved restrictively to specific cell type or associated ubiquitously with different human body compartments.

It was shown previously that dysfunctional expression of miRNAs is a frequent attribute of malignant behaviour. Nowadays, aberrant expression of specific miRNAs is associated with all cancer types.

Germline and somatic mutations as well as polymorphisms in the mRNAs targeted by miRNAs can also lead to cancer predisposition and progression.

Growing evidence points to miRNA being implicated in oncogenic processes, suggesting that miRNA expression profiling can distinguish tumours (according to diagnosis and cancer stages) more accurately than traditional gene expression analyses.

Small non-coding RNAs can play a dual role in tumorigenesis, acting as oncogenes (e.g. miR-155 of miR-17-92 cluster family members) or tumour suppressors (e.g. miR-15a and miR-16). To date, there are three proposed mechanisms implicating miRNA deregulation in cancer.

These processes involve chromosomal lesions at regions encoding miRNAs, failure in their biosynthetic pathway machinery, and epigenetic regulation.