miR‐21: a small multi‐faceted RNA

Abstract

• miR‐21 expression in cancer and other diseases • Mechanisms of miR‐21 elevation in cancer: multi‐level regulatory control • Transcriptional control • Post‐trancriptional regulation • miR‐21 functions in cancer • Identification of direct miR‐21 targets • miR‐21 in gliomas: targeting cell cycle, apoptosis and invasion • miR‐21 networking and feedback regulation • miR‐21 as a diagnostic and prognostic marker • Potential therapeutic target • Acknowledgements Abstract More than 1000 microRNAs (miRNAs) are expressed in human cells, some tissue or cell type specific, others considered as house‐keeping molecules. Functions and direct mRNA targets for some miRNAs have been relatively well studied over the last years. Every miRNA potentially regulates the expression of numerous protein‐coding genes (tens to hundreds), but it has become increasingly clear that not all miRNAs are equally important; diverse high‐throughput screenings of various systems have identified a limited number of key functional miRNAs over and over again. Particular miRNAs emerge as principal regulators that control major cell functions in various physiological and pathophysiological settings. Since its identification 3 years ago as the miRNA most commonly and strongly up‐regulated in human brain tumour glioblastoma [ 1 ], miR‐21 has attracted the attention of researchers in various fields, such as development, oncology, stem cell biology and aging, becoming one of the most studied miRNAs, along with let‐7, miR‐17–92 cluster (‘oncomir‐1’), miR‐155 and a few others. However, an miR‐21 knockout mouse has not yet been generated, and the data about miR‐21 functions in normal cells are still very limited. In this review, we summarise the current knowledge of miR‐21 functions in human disease, with an emphasis on its regulation, oncogenic role, targets in human cancers, potential as a disease biomarker and novel therapeutic target in oncology.