Exosomal miRNAs as cancer biomarkers and therapeutic targets.

Exosomal miRNAs as cancer biomarkers and therapeutic targets.
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DOI:
10.3402/jev.v5.31292
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发表时间:
2016
影响因子:
16
通讯作者:
Wilson C
Wilson C
中科院分区:
医学2区
文献类型:
--
作者:
Thind A;Wilson C

文献摘要

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癌细胞之间及其与周围和远处环境的相互交流是肿瘤生存、进展和转移的关键。外泌体在这一通信过程中发挥作用。微小RNA(miRNA)表达在肿瘤细胞中经常失调,并且可以通过从癌症患者的体液中分离的不同的外泌体miRNA(ex-miRNA)谱来反映。在这里,ex-miRNA作为癌症生物标志物和治疗靶点的潜力被严格分析。外泌体是体液中miRNA的稳定来源,但是,尽管有许多用于外泌体提取和miRNA定量的方法,但它们在临床环境中用于诊断的适用性是值得怀疑的。此外,外泌体转移的miRNA可以改变受体肿瘤和基质细胞的行为,以促进肿瘤发生,突出了癌症中细胞通讯的作用。然而,我们对外来体生物发生和miRNA加载机制的不完全理解意味着靶向外来体或其转移的miRNA的策略是有限的,并且不特异于肿瘤细胞。因此,如果要将ex-miRNA用于新型非侵入性诊断方法并作为癌症的治疗靶点,则需要两个进一步的进展:分离和检测ex-miRNA的方法,以及更好地了解它们在肿瘤细胞通讯中的生物起源和功能。
Intercommunication between cancer cells and with their surrounding and distant environments is key to the survival, progression and metastasis of the tumour. Exosomes play a role in this communication process. MicroRNA (miRNA) expression is frequently dysregulated in tumour cells and can be reflected by distinct exosomal miRNA (ex-miRNA) profiles isolated from the bodily fluids of cancer patients. Here, the potential of ex-miRNA as a cancer biomarker and therapeutic target is critically analysed. Exosomes are a stable source of miRNA in bodily fluids but, despite a number of methods for exosome extraction and miRNA quantification, their suitability for diagnostics in a clinical setting is questionable. Furthermore, exosomally transferred miRNAs can alter the behaviour of recipient tumour and stromal cells to promote oncogenesis, highlighting a role in cell communication in cancer. However, our incomplete understanding of exosome biogenesis and miRNA loading mechanisms means that strategies to target exosomes or their transferred miRNAs are limited and not specific to tumour cells. Therefore, if ex-miRNA is to be employed in novel non-invasive diagnostic approaches and as a therapeutic target in cancer, two further advances are necessary: in methods to isolate and detect ex-miRNA, and a better understanding of their biogenesis and functions in tumour-cell communication.