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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    • "MiR-21 is another DDR/SASP-related miRNA candidate. Its function is especially complex, since demonstration of its aberrant expression in numerous cancers has led to its designation as an 'onco-miR'; nonetheless it has also been shown as a key modulator in many inflammatory pathways[102,103]. MiR- 21 targets two important factors in the TLR signaling pathway, myeloid differentiation factor 88 (MyD88) and interleukin-1 receptor-associated kinase 1 (IRAK1). "
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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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