Feud or Friend? The Role of the miR-17-92 Cluster in Tumorigenesis.
MicroRNAs (miRNAs) are short, noncoding, and single-stranded RNA molecules that negatively regulate gene expression. They are evolutionarily conserved from plants to animals. During the last decade, miRNAs have been demonstrated as regulators in fundamental biological processes, including cell growth, proliferation, differentiation and apoptosis. By base pairing to the complementary sites in the mRNA of the target gene, miRNA can lead to repression of protein translation or cleavage of mRNA. Among over 700 miRNAs identified in the human genome, several of them were confirmed as 'oncomirs', which denote miRNAs associated with initiation and progression of cancers. Generally, depending on their target genes, these miRNAs function as tumor suppressors or oncogenes. However, the miR-17-92 cluster in the human genome, which encodes 7 mature microRNAs, has been validated as regulator showing both oncogenic and tumor suppressive properties. The miR-17-92 cluster targets mRNAs involved in distinct pathways so that it may exert opposing effects. The transcription factors E2Fs and c-Myc, which play critical roles in tumorigenesis, could interact with the cluster. The feedback loops, which are comprised of the transcription factors and the miR-17-92 cluster, weave a complex regulation net work of cancers. The duality of this cluster reflects the complexities of cancer progressions as well as the intricacies of the regulation network of miRNAs and their targets. With the help of the development of new experimental methods and bioinformatics, further researches on the miR-17-92 cluster and other oncomirs will give new insights into cancer diagnosis, therapy, and prognosis.
Xiang
Jie
J
School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, P.R. China.
Wu
Ji
J