Cowland Jack B, Hother Christoffer, Grønbaek Kirsten
The Granulocyte Research Laboratory, Department of Hematology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
APMIS. 2007 Oct;115(10):1090-106. doi: 10.1111/j.1600-0463.2007.apm_775.xml.x.
MicroRNAs (miRNAs) are a recently discovered group of small RNA molecules involved in the regulation of gene expression. Analogously to mRNAs, the non-protein-encoding pri-miRNAs are synthesized by RNA polymerase II and post-transcriptionally modified by addition of a 5'-cap and a 3'-poly (A) tail. Subsequently, the pri-miRNA undergoes a number of processing steps in the nucleus and cytoplasm, and ends up as a mature approximately 22 nt miRNA, which can exert its function by binding to the 3'-untranslated region of a subset of mRNAs. Binding of the miRNA to the mRNA results in a reduced translation rate and/or increased degradation of the mRNA. In this way a large number of cellular pathways, such as cellular proliferation, differentiation, and apoptosis, are regulated by mi-RNAs. As corruption of these pathways is the hallmark of many cancers, dysregulation of miRNA biogenesis or expression levels may lead to tumorigenesis. The mechanisms that alter the expression of miRNAs are similar to those that change the expression levels of mRNAs of tumor suppressor- and oncogenes, i.e. gross genomic aberrations, epigenetic changes, and minor mutations affecting the expression level, processing, or target-interaction potential of the miRNA. Furthermore, expression profiling of miRNAs has been found to be useful for classification of different tumor types. Taken together, miRNAs can be classified as onco-miRs or tumor suppressor-miRs, and may turn out to be potential targets for cancer therapy.
微小RNA(miRNA)是最近发现的一类参与基因表达调控的小RNA分子。与信使RNA(mRNA)类似,非蛋白质编码的初级miRNA(pri-miRNA)由RNA聚合酶II合成,并通过添加5'-帽和3'-聚腺苷酸尾进行转录后修饰。随后,pri-miRNA在细胞核和细胞质中经历一系列加工步骤,最终成为成熟的约22个核苷酸的miRNA,它可以通过与一部分mRNA的3'-非翻译区结合来发挥其功能。miRNA与mRNA的结合导致翻译速率降低和/或mRNA降解增加。通过这种方式,许多细胞途径,如细胞增殖、分化和凋亡,都受到miRNA的调控。由于这些途径的破坏是许多癌症的标志,miRNA生物合成或表达水平的失调可能导致肿瘤发生。改变miRNA表达的机制与改变肿瘤抑制基因和癌基因mRNA表达水平的机制相似,即基因组大片段畸变、表观遗传变化以及影响miRNA表达水平、加工或靶标相互作用潜力的微小突变。此外,已发现miRNA的表达谱分析有助于不同肿瘤类型的分类。综上所述,miRNA可分为致癌miRNA或肿瘤抑制miRNA,并且可能成为癌症治疗的潜在靶点。