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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    BioMed Research International 08/2014; 2014:591703. DOI:10.1155/2014/591703 · 2.71 Impact Factor
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