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结直肠癌细胞中 microRNA 的调控:从实验室到临床应用。

MicroRNA manipulation in colorectal cancer cells: from laboratory to clinical application.

机构信息

Department of Cancer Studies and Molecular Medicine, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, P O Box 65, Leicester LE2 7LX, United Kingdom.

出版信息

J Transl Med. 2012 Jun 20;10:128. doi: 10.1186/1479-5876-10-128.

Abstract

The development of Colorectal Cancer (CRC) follows a sequential progression from adenoma to the carcinoma. Therefore, opportunities exist to interfere with the natural course of disease development and progression. Dysregulation of microRNAs (miRNAs) in cancer cells indirectly results in higher levels of messenger RNA (mRNA) specific to tumour promoter genes or tumour suppressor genes. This narrative review aims to provide a comprehensive review of the literature about the manipulation of oncogenic or tumour suppressor miRNAs in colorectal cancer cells for the purpose of development of anticancer therapies. A literature search identified studies describing manipulation of miRNAs in colorectal cancer cells in vivo and in vitro. Studies were also included to provide an update on the role of miRNAs in CRC development, progression and diagnosis. Strategy based on restoration of silenced miRNAs or inhibition of over expressed miRNAs has opened a new area of research in cancer therapy. In this review article different techniques for miRNA manipulation are reviewed and their utility for colorectal cancer therapy has been discussed in detail. Restoration of normal equilibrium for cancer related miRNAs can result in inhibition of tumour growth, apoptosis, blocking of invasion, angiogenesis and metastasis. Furthermore, drug resistant cancer cells can be turned into drug sensitive cells on alteration of specific miRNAs in cancer cells. MiRNA modulation in cancer cells holds great potential to replace current anticancer therapies. However, further work is needed on tissue specific delivery systems and strategies to avoid side effects.

摘要

结直肠癌(CRC)的发展遵循从腺瘤到癌的顺序进展。因此,有机会干预疾病的自然发展和进展过程。癌细胞中 microRNAs(miRNAs)的失调间接导致肿瘤促进基因或肿瘤抑制基因的特异性信使 RNA(mRNA)水平升高。本综述旨在对关于在结直肠癌细胞中操纵致癌或肿瘤抑制 miRNAs 以开发抗癌疗法的文献进行全面综述。文献检索确定了描述体内和体外结直肠癌细胞中 miRNA 操纵的研究。还包括了研究,以提供 miRNA 在 CRC 发展、进展和诊断中的作用的最新信息。基于恢复沉默的 miRNAs 或抑制过度表达的 miRNAs 的策略为癌症治疗开辟了一个新的研究领域。在这篇综述文章中,我们回顾了不同的 miRNA 操纵技术,并详细讨论了它们在结直肠癌治疗中的应用。恢复与癌症相关的 miRNAs 的正常平衡可以导致肿瘤生长、细胞凋亡、阻断侵袭、血管生成和转移的抑制。此外,通过改变癌细胞中特定的 miRNAs,可以将耐药性癌细胞转变为对药物敏感的细胞。在癌细胞中调节 miRNA 具有取代当前抗癌疗法的巨大潜力。然而,需要进一步研究组织特异性传递系统和策略,以避免副作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e3b/3539910/167c24549e20/1479-5876-10-128-1.jpg

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