Mathupala Saroj P, Mittal Sandeep, Guthikonda Murali, Sloan Andrew E
Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
DNA Cell Biol. 2007 May;26(5):301-10. doi: 10.1089/dna.2006.0560.
Malignant brain tumors, including high-grade gliomas, are among the most lethal of all cancers. Despite considerable advances, including multi-modal treatments with surgery, radiotherapy, and chemotherapy, the overall prognosis remains dismal for patients diagnosed with these tumors. With the discovery of RNA interference (RNAi) for target-specific gene silencing via small interfering RNA (siRNA), a novel method to target malignant gliomas has been exposed, an endeavor that is aggressively being carried out in numerous laboratories. However, practical difficulties in tissue- or organ-specific targeting of therapeutic quantities of siRNA still preclude its applicability in a clinical setting. MicroRNA (miRNA), an endogenously expressed form of siRNA, not only presents an alternate method to induce RNAi in a given diseased tissue or organ, but also exposes a unique set of diagnostic markers that can be used to identify, and then differentiate between tumor grades. Thus, miRNA can be considered the cells' answer to siRNA. Discovered over a decade ago, miRNA is fast becoming recognized as crucial in regulating gene expression in cancers. Therein lies the therapeutic potential of miRNA, as it may now be possible to induce or inhibit RNAi in a given diseased cell population by controlling the cells' miRNA expression profile. This review outlines the potential of miRNA as a therapeutic strategy against high-grade gliomas, and also the technological hurdles that need to be addressed before this promising technique can be administered in a clinical setting.
恶性脑肿瘤,包括高级别胶质瘤,是所有癌症中致死性最高的肿瘤之一。尽管取得了显著进展,包括采用手术、放疗和化疗的多模式治疗,但对于被诊断患有这些肿瘤的患者而言,总体预后仍然不容乐观。随着通过小干扰RNA(siRNA)实现针对特定靶点基因沉默的RNA干扰(RNAi)技术的发现,一种针对恶性胶质瘤的新方法浮出水面,众多实验室都在积极开展这方面的研究。然而,在组织或器官特异性靶向递送治疗剂量的siRNA方面存在的实际困难,仍然限制了其在临床环境中的应用。微小RNA(miRNA)是siRNA的内源性表达形式,它不仅提供了一种在特定患病组织或器官中诱导RNAi的替代方法,还揭示了一组独特的诊断标志物,可用于识别并区分肿瘤级别。因此,miRNA可被视为细胞对siRNA的应对方式。miRNA在十多年前被发现,如今正迅速被公认为在癌症基因表达调控中起着关键作用。这正是miRNA的治疗潜力所在,因为现在有可能通过控制细胞的miRNA表达谱,在特定患病细胞群体中诱导或抑制RNAi。本综述概述了miRNA作为针对高级别胶质瘤的治疗策略的潜力,以及在将这项有前景的技术应用于临床之前需要克服的技术障碍。