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miR-21
MicroRNA 21, also named as has-mir-21 or miR-21, is a mammalian microRNA that is encoded by the MIR21 gene located on chromosome 17q23.2 within a protein-coding gene TMEM49 (vacuole membrane protein). Only mature microRNA can function, and miR-21 is generated by a serious cutting. Pri-miR-21, the long primary transcript of miR-21, is cut by the endonuclease Drosha to produce pre-miR-21 in the nucleus. Then, the pre-miR-21 is transferred into the cytoplasm where it is cut into a short RNA duplex by Dicer. After transcription, only one strand RNA (miR-21) is chosen to be as mature microRNA, which is loaded into RNA-induced silencing complex (microRNA ribonucleoprotein complex RISC) and headed to target mRNAs with complementary at 3'UTR.
Fig 1. Model of miR-21 network and feedback regulation. (Krichevsky, A., 2009)
The Roles of miR-21 in Cancer
A lot of studies have been illustrated that miR-21 participates in many pathological diseases such as cardiovascular diseases and carcinomas. miR-21 also functions as anti-apoptosis in many cells lines. It has been noted that miR-21 is overexpressed in some solid tumors, which include breast, prostate, colon and lung cancers. The role of miR-21 in the tumorigenesis is associated with the “oncogene addiction” that has the ability to maintain the malignant phenotype. Studies have indicated that overexpression of miR-21 is able to cause a pre-B malignant lymphoid-like phenotype, which means that miR-21 is a genuine oncogene.
miR-21 Marker of Cholangiocarcinoma
miR-21 is increased in the progression of some tumors. The elevated miR-21 always mean a poor survival in many cancers. miR-21 is overexpressed in human CCA (cholangiocarcinoma) and plays a significant role in the growth and metastasis of CCA by regulating a variety of target proteins. It can inhibit the expression of PDCD4 and TIMP3 (tissue inhibitor of metalloproteinases 3). And the expression of miR-21 inversely correlates with the metastasis suppressor RECK. In addition, miR-21 can decrease the expression of PTEN, a tumor suppressor, that plays an important role in cell proliferation. According to the studies, knockdown of Ars2 in CCA cells reduced the expression of miR-21 and increased the expression of PTEN and PDCD4, thus, decreasing cell proliferation and preventing tumor formation. Therefore, miR-21 has an important role to affect cell proliferation, metastasis, apoptosis and migration in cholangiocarcinoma. It is considered as the main biomarker for diagnosis and evaluating the prognosis in CCA patients.
miR-21 Marker of Asthmatic
More and more researches have suggested repeatedly that miRs are novel biomarkers for human allergic inflammatory diseases and a possible non-invasive method for diagnosis of such disease. Specifically, miRNA-21 has been reported to be up-regulated in many pathological conditions including cardiovascular diseases and cancer, and is also involved in the pathogenesis of childhood asthma. That is, microRNA-21 (miRNA-21/miR-21) has been found as a potential biomarker of childhood asthma and plays a significant role in asthma children by expression levels of miR-21 and its possible contribution in disease status.
As reported, miR-21 plays a significant role in asthma by showing that miR-21 expression could be stimulated actively by IL-13 and that miR-21 targets IL-12p35 mRNA and lowers IL-12 protein expression. IL-12p35 are important in balancing the TH2/TH1 skewing of T-helper cells; less IL-12 expression would partially account for the exaggerated TH2 response seen in asthma. It has been proposed that miR-21 can regulate as anti-inflammatory negative feedback by targeting a proinflammatory protein PDCD4 and downregulating IL-10 production. It has demonstrated miR-21 acts as an immunomodulating molecule and miR-21 up-regulation is an available signal for the diagnosis of childhood asthma. This suggests that miR-21 may be useful biomarkers for phenotyping respiratory diseases such as asthma, or for assessing underlying disease activity.
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Reference
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