- MicroRNA: Biogenetic and Functional Mechanisms and Involvements in Cell Differentiation and Cancer
miRNAs are expected to be potential targets of therapeutic strategies applied to drug discovery for a number of reasons. Firstly, in addition to the initiation and progression of tumor, miRNAs play critical roles in various biological pathways such as differentiation of adipocyte and insulin secretion and diseases such as diabetes and hepatitis. Therefore, the possibility that various human diseases are caused by abnormalities in miRNAs is indicated. Actually, miR-15 and miR-16 have been deleted or decreased in most cases of B-CLL and are identified as tumor suppressor genes (6, 7). Secondly, miRNA expression profiles are correlated with clinical severity of cancer malignancy, and because of this, miRNAs are expected to be powerful tools for cancer diagnosis (10). Thirdly, miRNAs are applicable in gene therapy. The expression of miRNAs can be introduced in vivo by using viral vectors and chemical modifications. Finally, antisense oligonucleotides are potent inhibitors of miRNA, and they can be applied to gene therapy. Actually, it was reported that introduction of 2'-O-methoxyethyl phosphorothioate antisense oligonucleotide of miR-122, which is abundant in the liver and regulates cholesterol and fatty-acid metabolism, decreases plasma cholesterol levels and improves liver steatosis in mice with diet-induced obesity (30). These findings indicate that miRNAs and the antisense oligonucleotides are potential targets for drug discovery.
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