[Application of microRNAs to Cancer Therapy]

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.