MiR-433-3p suppresses cell growth and enhances chemosensitivity by targeting CREB in human glioma
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Shupeng Sun1,*, Xiuyu Wang1,2,*, Xinnv Xu3,*, Hui Di4, Jixiang Du2, Bin Xu2, Qiong Wang1, Jinhuan Wang1
1Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin 300350, China
2The Graduate School, Tianjin Medical University, Tianjin 300070, China
3Key Laboratory for Critical Care Medicine of the Ministry of Health, Tianjin First Center Hospital, Tianjin 300192, China
4Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding 071000, China
*These authors have contributed equally to this work
Qiong Wang, email: [email protected]
Jinhuan Wang, email: [email protected]
Keywords: miR-433-3p, CREB, glioma, carcinogenesis, chemosensitivity
Received: June 16, 2016 Accepted: November 22, 2016 Published: December 03, 2016
Previous studies reported that miR-433 exerts function widely in human tumorigenesis and development. Here, we further investigate the potential role of miR-433 in glioma. Quantitative real-time PCR demonstrated that miR-433-3p and miR-433-5p were low expressed in glioma tissues and cell lines. Functional studies suggested that the overexpression of miR-433-3p suppressed proliferation, induced apoptosis and inhibited invasion and migration of human glioma cells. But the growth and metastasis of glioma cells were not significantly influenced by overexpression of miR-433-5p. In a xenograft model, we also showed that miR-433-3p had an inhibitory effect on the growth of glioma. Bioinformatics coupled with luciferase and western blot assays revealed that CREB is a direct target of miR-433-3p, and the overexpression of CREB can rescue the phenotype changes induced by miR-433-3p overexpression. Besides, miR-433-3p could increase chemosensitivity of glioma to temozolomide by targeting CREB in vitro and in vivo. Taken together, these results suggest that miR-433-3p may function as a potential marker in diagnostic and therapeutic target for glioma.
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