Abstract
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.
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Acknowledgments
This work was supported by the National Natural Science Foundation of China (81201978, No. 81172389, No. 81200362, No. 81372709, No. 81272792), the Jiangsu Province’s Natural Science Foundation (BK2012483, BK2010580), the Program for Advanced Talents within Six Industries of Jiangsu Province (2012-WSN-019), the National High Technology Research and Development Program of China (863) (2012AA02A508), International Cooperation Program (2012DFA30470), the Jiangsu Province’s Key Provincial Talents Program (RC2011051), the Jiangsu Province’s Key Discipline of Medicine (XK201117), the Jiangsu Provincial Special Program of Medical Science (BL2012028), the Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU, the Provincial Initiative Program for Excellency Disciplines, Jiangsu Province and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
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The authors declare no conflict of interest.
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Rui Zhang, Hui Luo, Shuai Wang, Zhengxin Chen and Lingyang Hua have contributed equally to this work.
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Zhang, R., Luo, H., Wang, S. et al. miR-622 suppresses proliferation, invasion and migration by directly targeting activating transcription factor 2 in glioma cells. J Neurooncol 121, 63–72 (2015). https://doi.org/10.1007/s11060-014-1607-y
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DOI: https://doi.org/10.1007/s11060-014-1607-y