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致癌miRNA:癌症中微小RNA的发现与进展

OncomiRs: the discovery and progress of microRNAs in cancers.

作者信息

Cho William C S

机构信息

Department of Clinical Oncology, Queen Elizabeth Hospital, Room 1305, 13/F, Block R, 30 Gascoigne Road, Kowloon, Hong Kong SAR, PR China.

出版信息

Mol Cancer. 2007 Sep 25;6:60. doi: 10.1186/1476-4598-6-60.

Abstract

microRNAs (miRNAs) are evolutionarily conserved, endogenous, small, noncoding RNA molecules of about 22 nucleotides in length that function as posttranscriptional gene regulators. They are deemed to play a crucial role in the initiation and progression of human cancer, and those with a role in cancer are designated as oncogenic miRNAs (oncomiRs). For example, miR-15 and miR-16 induce apoptosis by targeting Bcl2. miRNAs from the miR-17-92 cluster modulate tumor formation and function as oncogenes by influencing the translation of E2F1 mRNA. miR-21 modulates gemcitabine-induced apoptosis by phosphatase and tensin homolog deleted on chromosome 10-dependent activation of PI 3-kinase signaling. miR-34a acts as a suppressor of neuroblastoma tumorigenesis by targeting the mRNA encoding E2F3 and reducing E2F3 protein levels. The chromosomal translocations associating with human tumors disrupt the repression of High mobility group A2 by let-7 miRNA. In addition, the oncomiRs expression profiling of human malignancies has also identified a number of diagnostic and prognostic cancer signatures. This article introduces the roles of oncomiRs in neoplasm development, progression, diagnosis, prognostication, as well as their mechanism of actions on target mRNAs and the functional outcomes of their actions on mRNAs. The paper ends with a brief perspective to the future of oncomiRs.

摘要

微小RNA(miRNA)是进化上保守的内源性小非编码RNA分子,长度约为22个核苷酸,作为转录后基因调节因子发挥作用。它们被认为在人类癌症的发生和发展中起关键作用,那些在癌症中起作用的被指定为致癌miRNA(癌基因miRNA)。例如,miR-15和miR-16通过靶向Bcl2诱导细胞凋亡。来自miR-17-92簇的miRNA调节肿瘤形成,并通过影响E2F1 mRNA的翻译作为癌基因发挥作用。miR-21通过10号染色体上缺失的磷酸酶和张力蛋白同源物依赖的PI 3激酶信号激活来调节吉西他滨诱导的细胞凋亡。miR-34a通过靶向编码E2F3的mRNA并降低E2F3蛋白水平,作为神经母细胞瘤肿瘤发生的抑制剂。与人类肿瘤相关的染色体易位破坏了let-7 miRNA对高迁移率族蛋白A2的抑制作用。此外,人类恶性肿瘤的癌基因miRNA表达谱分析也确定了许多诊断和预后癌症标志物。本文介绍了癌基因miRNA在肿瘤发生、发展、诊断、预后中的作用,以及它们对靶mRNA的作用机制和对mRNA作用的功能结果。本文最后对癌基因miRNA的未来作了简要展望。

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