Regulation and function of miRNA-21 in health and disease

Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.
RNA biology (Impact Factor: 4.97). 09/2011; 8(5):706-13. DOI: 10.4161/rna.8.5.16154
Source: PubMed


The small regulatory RNA microRNA-21 (miR-21) plays a crucial role in a plethora of biological functions and diseases including development, cancer, cardiovascular diseases and inflammation. The gene coding for pri-miR-21 (primary transcript containing miR-21) is located within the intronic region of the TMEM49 gene. Despite pri-miR-21 and TMEM49 are overlapping genes in the same direction of transcription, pri-miR-21 is independently transcribed by its own promoter regions and terminated with its own poly(A) tail. After transcription, primiR- 21 is finally processed into mature miR-21. Expression of miR-21 has been found to be deregulated in almost all types of cancers and therefore was classified as an oncomiR. During recent years, additional roles of miR-21 in cardiovascular and pulmonary diseases, including cardiac and pulmonary fibrosis as well as myocardial infarction have been described. MiR-21 additionally regulates various immunological and developmental processes. Due to the critical functions of its target proteins in various signaling pathways, miR-21 has become an attractive target for genetic and pharmacological modulation in various disease conditions.

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    • "In addition, several transcriptional suppressors have also been reported, including NFI, C/EBPα, Gf1, and estrogen receptor (Fujita et al., 2008; Velu et al., 2009). MiR-21 expression is also regulated at the post-transcriptional level by signal transducers such as TGFb, BMP4, and SMADs (Kumarswamy et al., 2011). As such, the controlled or down-regulated expression of miR-21 is tightly associated with several fundamental biological and pathologic processes. "
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    • "In mice miR-21 is a limiting factor of immune response [7]. A tumorigenic role has also been highlighted for this miRNA [8]. Nevertheless, an extensive characterization of miR-21 targets is lacking and mechanistic details of its mode of action in T-lymphocytes are still unknown. "
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    ABSTRACT: microRNAs (miRNAs) are a class of small non-coding RNAs acting as post-transcriptional regulators of gene expression and play fundamental roles in regulating immune response and autoimmunity. We show that memory T-lymphocytes express higher levels of miR-21 compared to naïve T-lymphocytes and that miR-21 expression is induced upon TCR engagement of naïve T-cells. We identify bona fide miR-21 targets by direct immuno-purification and profiling of AGO2-associated mRNAs in Jurkat cells over-expressing miR-21. Our analysis shows that, in T-lymphocytes, miR-21 targets genes are involved in signal transduction. Coherently, TCR signalling is dampened upon miR-21 over-expression in Jurkat cells, resulting in lower ERK phosphorylation, AP-1 activation and CD69 expression. Primary human lymphocytes in which we impaired miR-21 activity, display IFN-γ production enhancement and stronger activation in response to TCR engagement as assessed by CD69, OX40, CD25 and CD127 analysis. By intracellular staining of the endogenous protein in primary T-lymphocytes we validate three key regulators of lymphocyte activation as novel miR-21 targets. Our results highlight an unexpected function of miR-21 as a negative modulator of signal transduction downstream of TCR in T-lymphocytes.
    Biochimie 10/2014; 107. DOI:10.1016/j.biochi.2014.09.021 · 2.96 Impact Factor
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    • "MiR-21 is well known to play an important role in normal and pathological processes including development, inflammation, cardiovascular function, and cancer. Many researchers found high expression of miR-21 in almost all types of solid cancer tissues including PCa and, therefore, it was classified as an oncomir [56]. MiR-21 targets tumor suppressor genes, such as phosphatase and tensin homolog (PTEN), tumor suppressor gene tropomyosin 1 (TPM1), programmed cell death 4 (PDCD4), maspin, and reversion-inducing cysteine-rich protein with Kazal motifs (RECK) [57–60]. "
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    ABSTRACT: Prostate cancer (PCa) is the second most common diagnosed malignant disease in men worldwide. Although serum PSA test dramatically improved the early diagnosis of PCa, it also led to an overdiagnosis and as a consequence to an overtreatment of patients with an indolent disease. New biomarkers for diagnosis, prediction, and monitoring of the disease are needed. These biomarkers would enable the selection of patients with aggressive or progressive disease and, hence, would contribute to the implementation of individualized therapy of the cancer patient. Since the FDA approval of the long noncoding PCA3 RNA-based urine test for the diagnosis of PCa patients, many new noncoding RNAs (ncRNAs) associated with PCa have been discovered. According to their size and function, ncRNAs can be divided into small and long ncRNAs. NcRNAs are expressed in (tumor) tissue, but many are also found in circulating tumor cells and in all body fluids as protein-bound or incorporated in extracellular vesicles. In these protected forms they are stable and so they can be easily analyzed, even in archival specimens. In this review, the authors will focus on ncRNAs as novel biomarker candidates for PCa diagnosis, prediction, prognosis, and monitoring of therapeutic response and discuss their potential for an implementation into clinical practice.
    BioMed Research International 08/2014; 2014:591703. DOI:10.1155/2014/591703 · 2.71 Impact Factor
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