Nuclear functions of mammalian MicroRNAs in gene regulation, immunity and cancer.
Nuclear functions of mammalian MicroRNAs in gene regulation, immunity and cancer.
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哺乳动物 MicroRNA 在基因调控、免疫和癌症中的核功能
DOI：
10.1186/s12943-018-0765-5
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发表时间：
2018-02-22
期刊：
影响因子：
37.3
通讯作者：
Tao Y
中科院分区：
文献类型：
--
作者：
Liu H;Lei C;He Q;Pan Z;Xiao D;Tao Y
microRNA（miRNAs）是一种内源性非编码RNA，含有约22个核苷酸。它们在各种生物过程中充当关键调节剂，并且它们的失调与许多疾病包括癌症和自身免疫性疾病有关。已经确定的是，miRNA的成熟发生在细胞质中，并且miRNA在细胞质中通过RNA诱导的沉默复合物（RISC）途径发挥转录后基因沉默（PTGS）。然而，大量的研究证实了成熟的miRNA存在于细胞核中，并阐明了其核质转运机制。此外，核内miRNAs的活性调控功能包括PTGS、转录基因沉默（TGS）和转录基因激活（TGA），其中miRNAs结合新生RNA转录本、基因启动子区或增强子区，并通过表观遗传途径发挥进一步的作用。基于已有的相互作用规则，开发了一些miRNA结合位点预测软件工具，并对这些工具进行了评价。此外，本文还对miRNA在免疫、肿瘤发生、肿瘤侵袭等方面的核功能进行了探讨和综述。作为miRNA作用的一个非经典方面，核miRNA补充了miRNA调控网络，并可应用于基于miRNA的治疗。
MicroRNAs (miRNAs) are endogenous non-coding RNAs that contain approximately 22 nucleotides. They serve as key regulators in various biological processes and their dysregulation is implicated in many diseases including cancer and autoimmune disorders. It has been well established that the maturation of miRNAs occurs in the cytoplasm and miRNAs exert post-transcriptional gene silencing (PTGS) via RNA-induced silencing complex (RISC) pathway in the cytoplasm. However, numerous studies reaffirm the existence of mature miRNA in the nucleus, and nucleus-cytoplasm transport mechanism has also been illustrated. Moreover, active regulatory functions of nuclear miRNAs were found including PTGS, transcriptional gene silencing (TGS), and transcriptional gene activation (TGA), in which miRNAs bind nascent RNA transcripts, gene promoter regions or enhancer regions and exert further effects via epigenetic pathways. Based on existing interaction rules, some miRNA binding sites prediction software tools are developed, which are evaluated in this article. In addition, we attempt to explore and review the nuclear functions of miRNA in immunity, tumorigenesis and invasiveness of tumor. As a non-canonical aspect of miRNA action, nuclear miRNAs supplement miRNA regulatory networks and could be applied in miRNA based therapies.
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