MicroRNA regulation of F-box proteins and its role in cancer.
MicroRNA regulation of F-box proteins and its role in cancer.
复制标题
DOI：
10.1016/j.semcancer.2015.09.016
复制
发表时间：
2016-02
影响因子：
14.5
通讯作者：
Pfeffer LM
中科院分区：
文献类型：
--
作者：
Wu ZH;Pfeffer LM
微小RNA（microRNAs，miRNAs）是一类内源性非编码小分子RNA，通过在转录后水平抑制基因表达而在肿瘤发生发展中发挥重要作用。一般而言，致癌miRNA在癌症中上调，而充当肿瘤抑制因子的miRNA下调，分别导致肿瘤抑制因子表达降低和癌基因表达上调。F-box蛋白作为SKP 1-CUL 1-F-box（SCF）-泛素连接酶复合物的底物识别组分，用于通过泛素-蛋白酶体系统降解其蛋白质靶。因此，F-box蛋白和miRNA都在转录后负调控靶基因的表达。由于每种miRNA都能够微调多个靶基因的表达，因此多个F-box蛋白可能被相同的miRNA抑制。同时，在不同的癌症类型中，一个F-box蛋白可以被多个miRNA调控。在这篇综述中，我们将重点关注miRNA介导的各种F-box蛋白的下调，由此产生的F-box蛋白底物的稳定性和这些过程对人类恶性肿瘤的影响。我们提供了关于miRNA：F-box蛋白轴如何调节癌症进展和转移的见解。我们还考虑了F-box蛋白在调节独立于泛素连接酶复合物的通路中的更广泛的作用，以及它如何影响肿瘤发生。miRNAs及其在癌症中调节的F-box蛋白是一个新兴领域，将为癌症治疗提供新的策略。
MicroRNAs (miRNAs) are small endogenous non-coding RNAs, which play critical roles in cancer development by suppressing gene expression at the post-transcriptional level. In general, oncogenic miRNAs are upregulated in cancer, while miRNAs that act as tumor suppressors are downregulated, leading to decreased expression of tumor suppressors and upregulated oncogene expression, respectively. F-box proteins function as the substrate-recognition components of the SKP1-CUL1-F-box (SCF)-ubiquitin ligase complex for the degradation of their protein targets by the ubiquitin-proteasome system. Therefore F-box proteins and miRNAs both negatively regulate target gene expression post-transcriptionally. Since each miRNA is capable of fine-tuning the expression of multiple target genes, multiple F-box proteins may be suppressed by the same miRNA. Meanwhile, one F-box proteins could be regulated by several miRNAs in different cancer types. In this review, we will focus on miRNA-mediated downregulation of various F-box proteins, the resulting stabilization of F-box protein substrates and the impact of these processes on human malignancies. We provide insight into how the miRNA: F-box protein axis may regulate cancer progression and metastasis. We also consider the broader role of F-box proteins in the regulation of pathways that are independent of the ubiquitin ligase complex and how that impacts on oncogenesis. The area of miRNAs and the F-box proteins that they regulate in cancer is an emerging field and will inform new strategies in cancer treatment.