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[微小RNA在癌症治疗中的应用]

[Application of microRNAs to Cancer Therapy].

作者信息

Iguchi Haruhisa, Ochiya Takahiro

机构信息

Section for Studies on Metastasis, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.

出版信息

Gan To Kagaku Ryoho. 2010 Mar;37(3):389-95.

PMID:20332672
Abstract

MicroRNAs (miRNAs) are small 20-22 nucleotide-long members of the non-protein-coding RNA family and cause an inhibition of translation and some degree of degradation of the target messenger RNAs (mRNAs) through binding to partially complementary sites, usually in the 3' untranslated regions of the target mRNAs. Therefore, miRNAs play pivotal roles as negative regulators of gene expression in a wide array of physiological processes. Recent observations reveal that many miRNAs have been implicated in various human cancers. Both losses and gains of miRNA function have been shown to contribute to cancer development through a variety of mechanisms. Over the past few years, miRNAs have been reported in human bodily fluids and represent new effective biomarkers. Particularly, in oncology, detection and monitoring of tumors are now becoming possible by the evaluation of tumor-derived secretory miRNAs. However, the secretory mechanism and biological function of extra cellular miRNAs remain unclear. Our ongoing studies show that secretory miRNAs in exosomes can be transferred and exert their function in living cells, suggesting that extra cellular miRNAs may mediate intercellular communication between cancer cells and their surrounding cells in a cancer microenvironment. The fact that several miRNA genes are dysregulated in multiple types of cancer indicates that significant pathways involved in tumorigenesis may have miRNAs as downstream targets. Thus, in tumors where miRNA genes are lost or amplified, miRNA mimetics or antagomirs, respectively, are considered as promising drugs to induce apoptosis and/or cell cycle arrest in cancer cells that depend on miRNA dysregulation for growth and survival. There is growing evidence that miRNA therapy could be a potent means to curtail tumor growth.

摘要

微小RNA(miRNA)是非蛋白质编码RNA家族中长度为20 - 22个核苷酸的小分子,通过与通常位于靶信使核糖核酸(mRNA)3'非翻译区的部分互补位点结合,导致靶mRNA的翻译抑制和一定程度的降解。因此,miRNA在广泛的生理过程中作为基因表达的负调节因子发挥着关键作用。最近的观察结果表明,许多miRNA与各种人类癌症有关。miRNA功能的丧失和获得均已显示通过多种机制促进癌症发展。在过去几年中,已在人体体液中报道了miRNA,它们代表了新的有效生物标志物。特别是在肿瘤学中,通过评估肿瘤来源的分泌性miRNA,现在可以对肿瘤进行检测和监测。然而,细胞外miRNA的分泌机制和生物学功能仍不清楚。我们正在进行的研究表明,外泌体中的分泌性miRNA可以转移并在活细胞中发挥其功能,这表明细胞外miRNA可能在癌症微环境中介导癌细胞与其周围细胞之间的细胞间通讯。多个miRNA基因在多种类型癌症中失调这一事实表明,参与肿瘤发生的重要途径可能以miRNA作为下游靶点。因此,在miRNA基因缺失或扩增的肿瘤中,miRNA模拟物或抗miR分别被认为是有前景的药物,可诱导依赖miRNA失调进行生长和存活的癌细胞凋亡和/或细胞周期停滞。越来越多的证据表明,miRNA疗法可能是抑制肿瘤生长的有效手段。

相似文献

1
[Application of microRNAs to Cancer Therapy].[微小RNA在癌症治疗中的应用]
Gan To Kagaku Ryoho. 2010 Mar;37(3):389-95.
2
MicroRNAs: novel regulators in the hallmarks of human cancer.微小RNA:人类癌症特征中的新型调节因子。
Cancer Lett. 2009 Nov 28;285(2):116-26. doi: 10.1016/j.canlet.2009.04.031. Epub 2009 May 22.
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MicroRNAs and cancer.微小RNA与癌症
APMIS. 2007 Oct;115(10):1090-106. doi: 10.1111/j.1600-0463.2007.apm_775.xml.x.
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microRNA expression in the eyes and their significance in relation to functions.眼睛中的微小RNA表达及其与功能的关系
Prog Retin Eye Res. 2009 Mar;28(2):87-116. doi: 10.1016/j.preteyeres.2008.11.003. Epub 2008 Nov 28.
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The roles of microRNA in cancer and apoptosis.微小RNA在癌症和细胞凋亡中的作用。
Biol Rev Camb Philos Soc. 2009 Feb;84(1):55-71. doi: 10.1111/j.1469-185X.2008.00061.x. Epub 2008 Nov 22.
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Role of miRNA in carcinogenesis and biomarker selection: a methodological view.微小RNA在致癌作用及生物标志物选择中的作用:方法学视角
Expert Rev Mol Diagn. 2007 Sep;7(5):569-603. doi: 10.1586/14737159.7.5.569.
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Genetic variations of microRNAs in human cancer and their effects on the expression of miRNAs.人类癌症中微小RNA的遗传变异及其对微小RNA表达的影响。
Carcinogenesis. 2008 Sep;29(9):1710-6. doi: 10.1093/carcin/bgn073. Epub 2008 Mar 19.
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MicroRNAs and apoptosis: implications in the molecular therapy of human disease.微小 RNA 与细胞凋亡:在人类疾病的分子治疗中的意义。
Clin Exp Pharmacol Physiol. 2009 Oct;36(10):951-60. doi: 10.1111/j.1440-1681.2009.05245.x. Epub 2009 Jun 29.
9
Expression profiling of microRNAs in cancer cells: technical considerations.癌细胞中微小RNA的表达谱分析:技术考量
Methods Mol Biol. 2008;439:179-90. doi: 10.1007/978-1-59745-188-8_12.
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MicroRNAs and cancer.微小RNA与癌症
Br J Surg. 2007 Jan;94(1):23-30. doi: 10.1002/bjs.5673.

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Med Oncol. 2012 Dec;29(4):2323-31. doi: 10.1007/s12032-011-0140-5. Epub 2011 Dec 31.