miR-21: a small multi-faceted RNA

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.

1

The consensus sequence of putative promoter region of miR-21. Conserved bases across vertebrates are shown in capitals and non-conserved bases or deletions are denoted by ‘n’. The arrow indicates the transcription start site of pri-miR-21. Conserved regions of various transcription factors are indicated by different colours. Two additional RE-1-binding elements responding to transcription factor REST are located at 7214 and 7100 bp upstream of the miR-21 transcription start site [38]. This figure is reproduced from reference 25.

2

Model of miR-21 network and feedback regulation. Maturation of miR-21 from pri-miR-21 is shown in the center of the model. miR-21 direct target genes are depicted on blue background. Genes shown on green background are regulated (probably indirectly) by miR-21 and are involved in miR-21 processing from pri-miR-21 to pre-miR-21.