Karsy Michael, Arslan Erol, Moy Fred
Department of Pathology, New York Medical College, Valhalla, NY, USA.
Genes Cancer. 2012 Jan;3(1):3-15. doi: 10.1177/1947601912448068.
Glioblastoma multiforme (GBM) is an aggressive grade IV astrocytoma with a 1-year median survival rate despite current treatment modalities. A thorough understanding of the vast genetic aberrations and signaling pathways involved in gliomagenesis as well as heterogeneous clinicopathological presentation remains elusive. The recent discovery of microRNAs (miRs) and their capability of simultaneously regulating multiple downstream genes may play a key role in explaining the complex mechanisms underlying GBM formation. miRs are 19 to 25 nucleotide non-protein-coding small RNA molecules involved in the suppression of mRNA translation. This review will summarize and discuss the most recent findings regarding miRs in GBM including downstream targets, functional effects, and therapeutic potentials. Specifically discussed miRs include miR-7, miR-9/miR-9*, miR-10a/miR-10a*/miR-10b, miR-15b, miR-17-92, miR-21, miR-26a, miR-34a, miR-93, miR-101, miR-124, miR-125a, miR-125b, miR-128, miR-137, miR-146b-5p, miR-153, miR-181a/miR-181b, miR-196a/miR-196b, miR-218, miR-221/miR-222, miR-296, miR-302-367, miR-326, miR-381, miR-451, and let-7a. In addition to gene regulatory roles, miRs have demonstrated significant diagnostic, prognostic, and therapeutic potential. These small molecules may both help in the understanding of GBM and in developing new therapeutic options.
多形性胶质母细胞瘤(GBM)是一种侵袭性IV级星形细胞瘤,尽管有当前的治疗方式,其1年中位生存率仍较低。对胶质瘤发生过程中涉及的大量基因畸变和信号通路以及异质性临床病理表现的全面了解仍然难以捉摸。最近发现的微小RNA(miR)及其同时调节多个下游基因的能力可能在解释GBM形成的复杂机制中起关键作用。miR是19至25个核苷酸的非蛋白质编码小RNA分子,参与抑制mRNA翻译。本综述将总结并讨论关于GBM中miR的最新发现,包括下游靶点、功能效应和治疗潜力。具体讨论的miR包括miR-7、miR-9/miR-9*、miR-10a/miR-10a*/miR-10b、miR-15b、miR-17-92、miR-21、miR-26a、miR-34a、miR-93、miR-101、miR-124、miR-125a、miR-125b、miR-128、miR-137、miR-146b-5p、miR-153、miR-181a/miR-181b、miR-196a/miR-196b、miR-218、miR-221/miR-222、miR-296、miR-302-367、miR-326、miR-381、miR-451和let-7a。除了基因调控作用外,miR还显示出显著的诊断、预后和治疗潜力。这些小分子可能有助于理解GBM并开发新的治疗选择。