MicroRNAs in Cancer Management: Big Challenges for Small Molecules

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 (miR-Base http://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 [1]. 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. Relevant examples of the role of miRNAs on specific cancer types are reported in this issue, with a focus on childhood acute lymphoblastic leukemia (original contribution by M. Duyu et al.), ovarian and cervical cancer (reviewed by Y. Kinose et al. and S. M. Díaz-González et al.), soft tissue sarcomas (reviewed by T. Fujiwara et al.), or medulloblastoma (reviewed by S. López-Ochoa et al.). 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. The review by A. Saumet and colleagues suitably introduces the current approaches and applications of miRNAs in cancer and human diseases, from expression analyses aimed at identifying miR-NAs potentially useful for tumor diagnosis or prognosis to the potential use of them as novel therapeutic agents. The opportunities and challenges of miRNAs as cancer biomarkers have been addressed in the …