Tili Esmerina, Michaille Jean-Jacques
Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, Biomedical Research Tower, 460 W 12th Avenue, Columbus, OH 43210, USA.
J Nucleic Acids. 2011;2011:102431. doi: 10.4061/2011/102431. Epub 2011 Aug 10.
MicroRNAs are short noncoding RNAs that regulate the expression of many target genes posttranscriptionally and are thus implicated in a wide array of cellular and developmental processes. The expression of miR-155 or miR-21 is upregulated during the course of the inflammatory response, but these microRNAs are also considered oncogenes due to their upregulation of expression in several types of tumors. Furthermore, it is now well established that inflammation is associated with the induction or the aggravation of nearly 25% of cancers. Therefore, the above microRNAs are thought to link inflammation and cancer. Recently, resveratrol (trans-3,4',5-trihydroxystilbene), a natural polyphenol with antioxidant, anti-inflammatory, and anticancer properties, currently at the stage of preclinical studies for human cancer prevention, has been shown to induce the expression of miR-663, a tumor-suppressor and anti-inflammatory microRNA, while downregulating miR-155 and miR-21. In this paper we will discuss how the use of resveratrol in therapeutics may benefit from the preanalyses on the status of expression of miR-155 or miR-21 as well as of TGFβ1. In addition, we will discuss how resveratrol activity might possibly be enhanced by simultaneously manipulating the levels of its key target microRNAs, such as miR-663.
微小RNA是短链非编码RNA,可在转录后调节许多靶基因的表达,因此参与了广泛的细胞和发育过程。在炎症反应过程中,miR-155或miR-21的表达会上调,但由于它们在几种肿瘤类型中的表达上调,这些微小RNA也被视为癌基因。此外,现已明确炎症与近25%的癌症的诱发或加重有关。因此,上述微小RNA被认为是炎症与癌症之间的联系纽带。最近,白藜芦醇(反式-3,4',5-三羟基芪),一种具有抗氧化、抗炎和抗癌特性的天然多酚,目前正处于人类癌症预防的临床前研究阶段,已被证明可诱导肿瘤抑制和抗炎微小RNA miR-663的表达,同时下调miR-155和miR-21。在本文中,我们将讨论白藜芦醇在治疗中的应用如何从对miR-155或miR-21以及TGFβ1表达状态的预分析中获益。此外,我们还将讨论如何通过同时调控其关键靶微小RNA(如miR-663)的水平来增强白藜芦醇的活性。