State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
PLoS One. 2012;7(11):e49570. doi: 10.1371/journal.pone.0049570. Epub 2012 Nov 20.
Migration-proliferation dichotomy is a common mechanism in gliomagenesis; however, an understanding of the exact molecular mechanism of this "go or grow" phenomenon remains largely incomplete. In the present study, we first found that microRNA-9 (miR-9) is highly expressed in glioma cells. MiR-9 inhibited the proliferation and promoted the migration of glioma cells by directly targeting cyclic AMP response element-binding protein (CREB) and neurofibromin 1 (NF1), respectively. Our data also suggested a migration-inhibitory role for CREB through directly regulating the transcription of NF1. Furthermore, we found that the transcription of miR-9-1 is under CREB's control, forming a negative feedback minicircuitry. Taken together, miR-9 inhibits proliferation but promotes migration, whereas CREB plays a pro-proliferative and anti-migratory role, suggesting that the CREB-miR-9 negative feedback minicircuitry plays a critical role in the determination of "go or grow" in glioma cells.
迁移-增殖二分法是胶质瘤发生的常见机制；然而，对于这种“去或生长”现象的确切分子机制仍知之甚少。在本研究中，我们首先发现 microRNA-9 (miR-9) 在神经胶质瘤细胞中高度表达。miR-9 通过直接靶向环磷酸腺苷反应元件结合蛋白 (CREB) 和神经纤维瘤 1 (NF1)，分别抑制神经胶质瘤细胞的增殖并促进其迁移。我们的数据还表明，CREB 通过直接调节 NF1 的转录来发挥迁移抑制作用。此外，我们发现 miR-9-1 的转录受 CREB 的控制，形成负反馈微环。总之，miR-9 抑制增殖但促进迁移，而 CREB 则发挥促增殖和抗迁移作用，表明 CREB-miR-9 负反馈微环在决定神经胶质瘤细胞的“去或生长”中起关键作用。
