Shi Xu-Bao, Tepper Clifford G, White Ralph W Devere
Department of Urology, University of California, Davis, School of Medicine, Sacramento, CA 95817, USA.
J Cell Mol Med. 2008 Sep-Oct;12(5A):1456-65. doi: 10.1111/j.1582-4934.2008.00420.x. Epub 2008 Jul 8.
Prostate cancer (CaP) is the most frequently diagnosed malignant tumour and the second leading cause of cancer deaths in American men. One of the most troubling aspects of this disease is that, after androgen ablation therapy, androgen-dependent cancer cells inevitably progress to an androgen-independent status, for which no effective treatment has yet been developed. To date, the mechanisms that underlie the occurrence and progression of CaP remain largely unknown. Recent studies suggest that microRNAs (miRNAs) are involved in human tumourigenesis. Some aberrantly expressed miRNAs have been discovered in CaP cell lines, xenografts and clinical tissues and these CaP-related miRNAs may play critical roles in the pathogenesis of CaP. This review provides an overview of current findings about aberrantly expressed miRNAs in CaP. Although a number of CaP-related miRNAs were discovered, to date, only five are characterized for their functionalities: three as oncogenes and two as tumour suppressors. To understand the mechanisms of miRNA action as oncogenes or tumour suppressors, mRNA targets of miRNAs were characterized. Oncogenic miRNAs down-regulate the expression of apoptosis-related genes, and tumour suppressor miRNAs target the proliferation-related genes. Importantly, there is evidence that CaP-related miRNAs are regulated through androgen signalling and that this regulation may contribute to the development of androgen independence. Due to the oncogenic or tumour-suppressive properties of CaP-related miRNAs, they are highly likely to be of clinical use first as biomarkers but more importantly as therapeutic targets for prostate cancer treatment in the near future.
前列腺癌(CaP)是美国男性中最常被诊断出的恶性肿瘤,也是癌症死亡的第二大主要原因。这种疾病最棘手的方面之一是,在雄激素剥夺治疗后,雄激素依赖性癌细胞不可避免地会发展为雄激素非依赖性状态,而针对这种状态尚未开发出有效的治疗方法。迄今为止,CaP发生和发展的潜在机制在很大程度上仍然未知。最近的研究表明,微小RNA(miRNA)参与了人类肿瘤的发生。在CaP细胞系、异种移植瘤和临床组织中发现了一些异常表达的miRNA,这些与CaP相关的miRNA可能在CaP的发病机制中起关键作用。本综述概述了目前关于CaP中异常表达的miRNA的研究结果。尽管发现了许多与CaP相关的miRNA,但迄今为止,只有五种miRNA的功能得到了表征:三种作为癌基因,两种作为肿瘤抑制因子。为了了解miRNA作为癌基因或肿瘤抑制因子的作用机制,对miRNA的mRNA靶标进行了表征。致癌性miRNA下调凋亡相关基因的表达,而肿瘤抑制性miRNA靶向增殖相关基因。重要的是,有证据表明与CaP相关的miRNA通过雄激素信号通路进行调控,并且这种调控可能有助于雄激素非依赖性的发展。由于与CaP相关的miRNA具有致癌或肿瘤抑制特性,它们极有可能首先作为生物标志物用于临床,但更重要的是在不久的将来作为前列腺癌治疗的靶点。