miR-622 suppresses proliferation, invasion and migration by directly targeting activating transcription factor 2 in glioma cells
miR-622 suppresses proliferation, invasion and migration by directly targeting activating transcription factor 2 in glioma cells
复制标题
miR-622通过直接靶向激活神经胶质瘤细胞中的转录因子2来抑制增殖、侵袭和迁移
DOI：
10.1007/s11060-014-1607-y
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发表时间：
2015-01-01
影响因子：
3.9
通讯作者：
Wang, Huibo
中科院分区：
文献类型：
--
作者：
Zhang, Rui;Luo, Hui;Wang, Huibo
恶性胶质瘤是成人中最常见和最具破坏性的原发性脑肿瘤。肿瘤细胞迅速侵入邻近的正常脑组织是治疗失败的主要原因，但调节这一过程的机制仍然知之甚少。microRNA是近年来发现的一种通过多种信号通路调控肿瘤侵袭和转移的分子。在本研究中，我们发现miR-622在胶质瘤组织和细胞系中显著下调。功能实验表明，增加miR-622表达减少胶质瘤细胞的侵袭和迁移，而减少miR-622表达增强细胞的侵袭和迁移。此外，转录激活因子2（ATF 2），一个重要的转录因子，调节肿瘤的侵袭，被确定为miR-622的直接目标。使用小干扰RNA敲除ATF 2可以重现miR-622的抗侵袭功能，而恢复ATF 2表达则会减弱胶质瘤细胞中miR-622的功能。此外，临床数据表明，miR-622和ATF 2在胶质瘤标本中呈负表达。我们的研究结果提供了对miR-622在肿瘤侵袭和迁移中的特定生物学行为的深入了解。靶向miR-622/ATF 2轴是阻断胶质瘤侵袭的一种新的治疗方法。
Malignant gliomas are the most common and devastating primary brain tumors in adults. The rapid invasion of tumor cells into the adjacent normal brain tissues is a major cause of treatment failure, yet the mechanisms that regulate this process remain poorly understood. MicroRNAs have recently emerged as regulators of invasion and metastasis by acting on multiple signaling pathways. In this study, we found that miR-622 is significantly downregulated in glioma tissues and cell lines. Functional experiments showed that increased miR-622 expression reduced glioma cell invasion and migration, whereas decreased miR-622 expression enhanced cell invasion and migration. Moreover, activating transcription factor 2 (ATF2), an important transcription factor that regulate tumor invasion, was identified as a direct target of miR-622. Knockdown of ATF2 using small interefering RNA recapitulated the anti-invasive function of miR-622, whereas restoring the ATF2 expression attenuated the function of miR-622 in glioma cells. Furthermore, clinical data indicated that miR-622 and ATF2 were inversely expressed in glioma specimens. Our findings provide insight into the specific biological behavior of miR-622 in tumor invasion and migration. Targeting miR-622/ATF2 axis is a novel therapeutic approach for blocking glioma invasion.