MicroRNAs: non coding pleiotropic factors in development, cancer prevention and treatment

One of the most important advance obtained from transcriptome analysis in recent years is the discovery of a series of noncoding RNA (ncRNA) families, with regulatory roles in several biological processes, that are actively transcribed from the genome of many organisms. Among them microRNAs (miRNAs) are small regulatory, single-stranded, RNA molecules (19-25 nucleotides in length) that are generated from hairpin primary transcripts [1]. In the cytoplasm, the mature miRNA molecule, through a limited base-pairing complementary sequences interaction, destabilizes or blocks the translation of their phylogenetically conserved target mRNAs transcripts [2]. Following the identification of a functional miRNAs pathway in C. elegans, miRNAs contribution to development, cell fate determination and physiological tissue homeostasis in mammals has rapidly emerged [3]. MiRNAs exhibit a developmental stage- and tissue-specific expression pattern and are present in complex regulatory circuits to regulate stem cells function, tissue differentiation and maintenance of cell identity during embryogenesis and adult life [4]. Recently, the deregulation of miRNAs expression and activity has been correlated with the pathogenesis of various human diseases and cancer. In cancer, the loss of tumour suppressive miRNAs enhances the expression of target oncogenes, whereas increased expression of oncogenic miRNAs can repress target tumour suppressor genes [5, 6]. This new wealth of knowledge points to miRNAs as being novel cancer genes and biomarkers relevant to the pathogenesis, diagnosis and prognosis of disease that may be useful in the management of human cancer. Moreover, the localization of non-random chromosomal abnormalities and other types of genetic alterations at miRNA genomic regions observed in several types of cancer cells underline the contribution of the deregulation of miRNAs expression to malignancy processes [7]. Advances in expression technologies have facilitated the high-throughput analysis of small RNAs, identifying novel miRNAs and showing that these genes may be aberrantly expressed in various human tumors [8]. Hence, a new molecular taxonomy of human cancers based on miRNAs expression profiling has been proposed. Indeed, it was recently found that miRNAs profiles are more informative than messenger RNA profiles and could classify poorly differentiated tumors since they better reflect the developmental lineage and differentiation state of cancer. Different wide screening approaches performed to establish miRNAs expression profiles showed a unique miRNAs signature, relevant to the pathogenesis, diagnosis and prognosis of disease that may be useful in the management of human cancer. Summarizing, miRNAs expression and regulation are emerging in several normal and pathological processes ranging from the control of embryonic stem cell commitment to the deregulation of cell fate determination and the molecular pathogenesis of human cancer. The aim of this issue is to review the functional roles of microRNA pathways in the establishment and progression of human diseases with a particular attention to the identification of miRNAs signatures as innovative cancer biomarkers for the management and prevention of human cancers.