Department of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Hefei, China.
Anhui Province Key Laboratory of Major Autoimmune Diseases, Hefei, China.
J Cell Physiol. 2018 Jan;234(1):158-170. doi: 10.1002/jcp.26775. Epub 2018 Aug 3.
Glioma is the most aggressive primary brain tumor and is notorious for resistance to chemoradiotherapy. Although its associated mechanisms are still not completely understood, Notch signaling, an evolutionarily conserved pathway, appears to be the key processes involved. Nevertheless, its mechanisms are sophisticated, due to a variety of targets and signal pathways, especially microRNA. MicroRNAs, which are small noncoding regulatory RNA molecules, have been proposed as one of the key mechanisms in glioma pathogenesis. Among the known glioma associated microRNA, microRNA-129, microRNA-34 family, and microRNA-326 have been shown to influence the progress of glioma through Notch signaling. Evidence also indicates that recurrence is due to development or persistence of the glioma stem-like cells and active angiogenesis, which are tightly regulated by a variety of factors, including Notch signaling. In this review, we summarize the recent progress regarding the functional roles of Notch signaling in glioma, including Notch ligand, microRNA, intracellular crosstalk, glioma stem-like cells and active angiogenesis and explore their clinical implications as diagnostic or prognostic biomarkers and molecular therapeutic targets for glioma.
神经胶质瘤是最具侵袭性的原发性脑肿瘤，以对放化疗的耐药性而臭名昭著。尽管其相关机制尚不完全清楚，但 Notch 信号通路作为一个进化上保守的通路，似乎是涉及的关键过程。然而，由于存在多种靶点和信号通路，尤其是 microRNA，其机制非常复杂。microRNA 是一种小型非编码调节 RNA 分子，被认为是神经胶质瘤发病机制中的关键机制之一。在已知的与神经胶质瘤相关的 microRNA 中，microRNA-129、microRNA-34 家族和 microRNA-326 已被证明通过 Notch 信号通路影响神经胶质瘤的进展。有证据表明，复发是由于神经胶质瘤干细胞样细胞的发展或持续存在以及活跃的血管生成，这些过程受到包括 Notch 信号通路在内的多种因素的严格调控。在这篇综述中，我们总结了 Notch 信号通路在神经胶质瘤中的功能作用的最新进展，包括 Notch 配体、microRNA、细胞内串扰、神经胶质瘤干细胞样细胞和活跃的血管生成，并探讨了它们作为神经胶质瘤的诊断或预后生物标志物和分子治疗靶点的临床意义。
