MicroRNA Signatures in Human Cancers

Top Cited Papers
Publisher Website
Google Scholar
Abstract
MicroRNAs (miRNAs) located in genomic regions amplified in cancers (such as the miR-17–92 cluster) function as oncogenes, whereas miRNAs located in portions of chromosomes deleted in cancers (such as the miR-15a–miR-16-1 cluster) function as tumour suppressors. Abnormal expression of miRNAs has been found in both solid and haematopoietic tumours by various genome-wide techniques (including different microarray platforms or bead-based flow cytometry). The abnormally expressed miRNAs in human cancers target transcripts of essential protein-coding genes involved in tumorigenesis, such as the Ras oncogenes by let-7 family members, the BCL2 anti-apoptotic gene by the miR-15a–miR-16-1 cluster, the E2F1 transcription factor by the miR-17–92 cluster or the BCL6 anti-apoptotic gene by miR-127. MiRNA expression fingerprints correlate with clinical and biological characteristics of tumours, including tissue type, differentiation, aggression and response to therapy. The fact that consistent abnormal expression of the precursor miRNA, but not of the correspondent active molecule, is found in various types of cancers, raises the possibility that the 'non-active' part of the miRNA molecule could have 'independent' and as yet unknown functions that could be important in tumorigenesis. Germline sequence abnormalities were identified in miRNA genes and transcripts, and in targeted sequences in messenger RNAs that are known to be targets of miRNAs. Furthermore, as each miRNA has many targets, inherited minor variations in miRNA expression could have important consequences for the expression of various protein-coding genes involved in malignant transformation. Therefore, it is tempting to propose that both these phenomenons are involved in familial predisposition to cancer.