Abstract. MicroRNAs (miRs) are a class of single-stranded RNA molecules of 15-27 nucleotides in length that regulate gene expression at the post-translational level. miR-21 is one of the earliest identified cancer-promoting 'oncomiRs', targeting numerous tumor suppressor genes associated with proliferation, apoptosis and invasion. The regulation of miR-21 and its role in carcinogenesis have been extensively investigated. Recent studies have focused on the diagnostic and prognostic value of miR-21 as well as its implication in the drug resistance of human malignancies. The further use of miR-21 as a biomarker and target for cancer treatments is likely to improve the outcome for patients with cancer. The present review highlights recent findings associated with the importance of miR-21 in hematological and non-hematological malignancies.
IntroductionMicroRNAs (miRs) are a class of naturally occurring short non-coding RNA molecules of 15-27 nucleotides in length that regulate eukaryotic gene expression at the post-transcriptional level. Almost 2,000 human miRNAs have been identified through cloning and/or sequence analysis (1). They have key regulatory roles in the development, differentiation and apoptosis of normal cells, as well as in the determination of the final phenotype of cancer cells, affecting carcinogenesis and metastatic potential (2). miR-21 is an abundantly expressed miRNA in mammalian cells, whose upregulation is associated with numerous types of cancer (3,4). By generation of a conditional miR-21 knock-in mouse, it was demonstrated that miR-21 functions as an oncogene with its overexpression resulting in malignant B-cell lymphoma (5). Indeed, miR-21 was found to be the only consistently upregulated miRNA in a study that profiled 540 clinical samples from cancer patients (6). The majority of studies on miR-21 have focused on its role in carcinogenesis and its clinical application. miR-21 is also expressed in hematopoietic cells of the immune system, including B/T cells, monocytes, macrophages and dendritic cells. High miR-21 levels are, therefore, considered to be a marker of immune cell activation (7). Regarding pathological necrosis, miR-21 enhances cellular necrosis by negatively regulating tumor suppressor genes associated with the death receptor-mediated intrinsic apoptotic pathway (8).
Biological function of miR-21The biological functions of various miRNAs, including miR-21, have been extensively investigated and miR-21 is