MicroRNAs in Cancer Management: Big Challenges for Small Molecules
Gandellini P, Giovannetti E, Nicassio F.
Biomed Res Int. 2015;2015:982156. doi: 10.1155/2015/982156. Epub 2015 Mar 24.
In the last decade, the scientific community has been shaken by what we call the “noncoding revolution.” We have witnessed the discovery of an increasing amount of RNA molecules, which play a critical role in normal physiology as well as disease, without providing any protein product. The smallest regulatory RNA species, known as the ~22 nucleotide-long microRNAs (miRNAs), were at the forefront of such a revolution.
According to the last release of miRNA database (miRBase www.mirbase.org release 21) more than 35,000 miRNA species have been identified, of which a total of more than 2,500 mature miRNAs exist only in humans. Since their first discovery in C. elegans in 1993, it has become clear that these tiny molecules have an enormous regulatory potential, being able to exert negative posttranscriptional regulation on hundreds of protein coding genes, even simultaneously, and ultimately act as master regulators of entire biological processes.
Besides their role in development, the involvement of miRNAs in human disease, and cancer in particular, has attracted major attention. In fact, deregulated miRNA expression could lead to aberrant expression of targeted oncogenes or tumor suppressors, thus resulting in tumor development and progression. Accordingly, altered expression of miRNAs has been observed in almost every tumor type, including haematological malignancies, carcinomas, sarcomas, and central nervous system neoplasms.
The unique pattern of altered miRNA expression provides a fingerprint that may serve for cancer diagnosis and prediction of patient’s prognosis or response to treatment. In addition, a number of miRNAs have been shown to directly participate in tumorigenesis by acting as “oncoMirs” or “tumor suppressive miRNAs,” thus becoming potential key targets or tools for anticancer therapy.
Due to their nature as physiological molecules able to control multiple genes at the same time, miRNAs are also considered as very promising therapeutic targets or tools. As tumors typically evade cancer treatment by acquiring secondary mutations on targeted proteins, it appears more difficult for a tumor to escape from miRNA effects, which are directed on multiple proteins at the same time. Controlling the delivery and activity of miRNA-modulating agents into specific tissues or organs still appears as the “the big challenge,” albeit a number of promising approaches are under validation.
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