Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, PR China.
Oncogene. 2012 Aug 23;31(34):3866-74. doi: 10.1038/onc.2011.551. Epub 2011 Dec 5.
Glioma is the most common and fatal primary brain tumor. Thus far, therapeutic strategies to efficiently and specifically antagonize glioma are limited and poorly developed. Here we report that glia-enriched miR-135a, a microRNA that is dramatically downregulated in malignant glioma and correlated with the pathological grading, is capable of inducing mitochondria-dependent apoptosis of malignant glioma by regulating various genes including STAT6, SMAD5 and BMPR2, as well as affecting the signaling pathway downstream. Moreover, this lethal effect is selectively towards malignant glioma cells, but not neurons and glial cells, through a novel mechanism. Our findings suggest an important role of miR-135a in glioma etiology and provide a potential candidate for malignant glioma therapy.
神经胶质瘤是最常见和最致命的原发性脑肿瘤。到目前为止,有效和特异性拮抗神经胶质瘤的治疗策略有限且尚未得到充分发展。在这里,我们报告说,富含神经胶质的 miR-135a 是一种在恶性神经胶质瘤中显著下调且与病理分级相关的 microRNA,能够通过调节包括 STAT6、SMAD5 和 BMPR2 在内的各种基因以及影响下游信号通路来诱导恶性神经胶质瘤的线粒体依赖性细胞凋亡。此外,通过一种新的机制,这种致死效应是选择性地针对恶性神经胶质瘤细胞,而不是神经元和神经胶质细胞。我们的研究结果表明 miR-135a 在神经胶质瘤发病机制中起重要作用,并为恶性神经胶质瘤的治疗提供了一个潜在的候选药物。