miRNA genetic alterations in human cancers

MicroRNAs (miRNAs) are endogenous, non-coding, small RNAs, which negatively regulate gene expression in a sequence-specific manner via translational repression and/or mRNA degradation. Their discovery revealed a new and exciting aspect of post-transcriptional gene regulation that is universally involved in cellular homeostasis. Importantly, the advent of miRNAs added another level of complication in the already complex regulatory networks of the cell, undermining that RNA molecules in general, should be considered gene regulators of equal importance with proteins. Recently, the scientific community drew attention to the miRNA field for an additional reason: an increasing line of evidence indicated that miRNA genes are tightly connected with the process of tumorigenesis. Indeed, several miRNAs have already been demonstrated to behave as oncogenes or tumor suppressor genes in many types of cancer. Even though the underlying mechanisms by which miRNAs can destabilize the normal cellular processes, promoting cell transformation and tumor progression, are not well understood, genetic and epigenetic alterations most probably play a critical role. Significant technologic advances facilitated the profiling of the miRNA expression patterns in normal and cancer tissues and discovered an unexpected greater reliability of miRNA expression signatures in classifying cancer types than the respective signatures of protein-coding genes. Along with this extraordinary diagnostic potential, miRNAs have also proved their prognostic value in predicting clinical behaviors of cancer patients. The aim of this review is to describe miRNA expression and how its deregulation is involved in the pathophysiology of human cancers.