Garofalo Michela, Leva Gianpiero Di, Croce Carlo M
The Ohio State University, 992, Biomedical Research Tower, 460 W 12th Avenue, Columbus, OH 43210.
Curr Pharm Des. 2014;20(33):5328-35. doi: 10.2174/1381612820666140128211346.
MicroRNAs (miRNAs) are endogenously expressed and evolutionarily conserved small non-coding RNAs, which regulate gene expression. Several studies have shown that they are involved in fundamental biological processes, such as proliferation and apoptosis. MicroRNA dysregulation plays an important role in cancer onset and progression where miRs can function as both tumor promoters (oncomiRs) or tumor suppressors by targeting numerous biomolecules that are important in carcinogenesis. MicroRNA molecules are already entering the clinic as diagnostic and prognostic biomarkers for patient stratification and also as therapeutic targets and agents. Their role as biomarkers and therapeutic targets is appealing but several obstacles have as yet limited our ability to translate this potential into a clinical reality. This review provides a comprehensive overview of miRNAs with established functional relevance in cancer. Furthermore, approaches towards therapeutic miRNA-based intervention are discussed. Those include viral or non-viral approaches of miRNA replacement therapy in the case of tumor-suppressing miRNAs and strategies for the inhibition of oncogenic miRNAs.
微小RNA(miRNA)是内源性表达且在进化上保守的小非编码RNA,其可调控基因表达。多项研究表明,它们参与增殖和凋亡等基本生物学过程。微小RNA失调在癌症的发生和发展中起重要作用,其中miR可通过靶向众多在致癌过程中重要的生物分子,发挥肿瘤促进因子(致癌miR)或肿瘤抑制因子的作用。微小RNA分子已作为诊断和预后生物标志物用于患者分层,也作为治疗靶点和药物进入临床。它们作为生物标志物和治疗靶点的作用很有吸引力,但目前一些障碍限制了我们将这种潜力转化为临床现实的能力。本综述全面概述了在癌症中具有已确立功能相关性的miRNA。此外,还讨论了基于miRNA的治疗性干预方法。这些方法包括在肿瘤抑制性miRNA情况下的病毒或非病毒miRNA替代疗法,以及抑制致癌性miRNA的策略。