Iguchi Haruhisa, Ochiya Takahiro
Section for Studies on Metastasis, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Gan To Kagaku Ryoho. 2010 Mar;37(3):389-95.
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.
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。