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异常的 CXCR4 调节通过异常的 microRNA 靶向相互作用发生在癌症中。

Aberrant regulation of CXCR4 in cancer via deviant microRNA-targeted interactions.

机构信息

Department of Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri 65212, USA.

Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago, Chicago, Il 60637, USA.

出版信息

Epigenetics. 2022 Dec;17(13):2318-2331. doi: 10.1080/15592294.2022.2118947. Epub 2022 Sep 6.

Abstract

CXCR4 is involved in many facets of cancer, including being a major player in establishing metastasis. This is in part due to the deregulation of CXCR4, which can be attributed to many genetic and epigenetic mechanisms, including aberrant microRNA-CXCR4 interaction. MicroRNAs (miRNAs) are a type of small non-coding RNA that primarily targets the 3' UTR of mRNA transcripts, which in turn suppresses mRNA and subsequent protein expression. In this review, we reported and characterized the many aberrant miRNA-CXCR4 interactions that occur throughout human cancers. In particular, we reported known target sequences located on the 3' UTR of CXCR4 transcripts that tumour suppressor miRNAs bind and therefore regulate expression by. From these aberrant interactions, we also documented affected downstream genes/pathways and whether a particular tumour suppressor miRNA was reported as a prognostic marker in its respected cancer type. In addition, a limited number of cancer-causing miRNAs coined 'oncomirs' were reported and described in relation to CXCR4 regulation. Moreover, the mechanisms underlying both tumour suppressor and oncomir deregulations concerning CXCR4 expression were also explored. Furthermore, the miR-146a-CXCR4 axis was delineated in oncoviral infected endothelial cells in the context of virus-causing cancers. Lastly, miRNA-driven therapies and CXCR4 antagonist drugs were discussed as potential future treatment options in reported cancers pertaining to deregulated miRNA-CXCR4 interactions.

摘要

CXCR4 涉及癌症的多个方面,包括成为转移的主要参与者。这在一定程度上是由于 CXCR4 的失调,这可以归因于许多遗传和表观遗传机制,包括异常的 microRNA-CXCR4 相互作用。MicroRNAs(miRNAs)是一种小型非编码 RNA,主要靶向 mRNA 转录物的 3'UTR,从而抑制 mRNA 和随后的蛋白质表达。在这篇综述中,我们报告并描述了在人类癌症中发生的许多异常 miRNA-CXCR4 相互作用。特别是,我们报告了位于 CXCR4 转录物 3'UTR 上的已知靶序列,肿瘤抑制 miRNA 结合并因此调节表达。从这些异常相互作用中,我们还记录了受影响的下游基因/途径,以及特定的肿瘤抑制 miRNA 是否被报道为其相应癌症类型的预后标志物。此外,还报道了有限数量的致癌 miRNA,称为“oncomirs”,并与 CXCR4 的调节有关。此外,还探讨了与 CXCR4 表达相关的肿瘤抑制 miRNA 和 oncomir 失调的潜在机制。此外,还描述了在致癌病毒感染的内皮细胞中 miR-146a-CXCR4 轴的情况。最后,讨论了 miRNA 驱动的治疗和 CXCR4 拮抗剂药物作为与失调的 miRNA-CXCR4 相互作用相关的报告癌症的潜在未来治疗选择。

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