MicroRNA Processing and Human Cancer.

MicroRNA Processing and Human Cancer.
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DOI:
10.3390/jcm4081651
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发表时间:
2015-08-21
影响因子:
3.9
通讯作者:
Calin GA
Calin GA
中科院分区:
医学2区
文献类型:
--
作者:
Ohtsuka M;Ling H;Doki Y;Mori M;Calin GA

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microRNA(miRNAs)是一类长度为20 ~ 25个核苷酸的短链非编码RNA,主要通过与靶基因非翻译区(3′UTR)3′端的特异性序列结合来调控基因的转录后表达。自从第一份关于miRNAs在癌症中的临床相关性的报告以来,许多miRNAs已被证明作为癌基因,而其他的则作为肿瘤抑制因子。此外,由于miRNA加工因子的改变,已经在多种人类癌症类型中观察到全局miRNA失调。如先前的研究所示,顺序的miRNA加工可以分为三个步骤:在细胞核中由RNA酶加工;由Exportin-5(XPO 5)从细胞核运输;以及在细胞质中由RNA诱导的沉默复合物(RISC)加工。通过基因组突变、异常表达或其他方式改变miRNA加工基因,可显著影响癌症的发生、进展和转移。在这篇综述中,我们专注于miRNA的生物发生,重点是miRNA加工因子在人类癌症中的潜力。
MicroRNAs (miRNAs) are short non-coding RNAs of 20 to 25 nucleotides that regulate gene expression post-transcriptionally mainly by binding to a specific sequence of the 3′ end of the untranslated region (3′UTR) of target genes. Since the first report on the clinical relevance of miRNAs in cancer, many miRNAs have been demonstrated to act as oncogenes, whereas others function as tumor suppressors. Furthermore, global miRNA dysregulation, due to alterations in miRNA processing factors, has been observed in a large variety of human cancer types. As previous studies have shown, the sequential miRNA processing can be divided into three steps: processing by RNAse in the nucleus; transportation by Exportin-5 (XPO5) from the nucleus; and processing by the RNA-induced silencing complex (RISC) in the cytoplasm. Alteration in miRNA processing genes, by genomic mutations, aberrant expression or other means, could significantly affect cancer initiation, progression and metastasis. In this review, we focus on the biogenesis of miRNAs with emphasis on the potential of miRNA processing factors in human cancers.