MiR-433-3p suppresses cell growth and enhances chemosensitivity by targeting CREB in human glioma

// Shupeng Sun 1, * , Xiuyu Wang 1, 2, * , Xinnv Xu 3, * , Hui Di 4 , Jixiang Du 2 , Bin Xu 2 , Qiong Wang 1 , Jinhuan Wang 1 1 Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin 300350, China 2 The Graduate School, Tianjin Medical University, Tianjin 300070, China 3 Key Laboratory for Critical Care Medicine of the Ministry of Health, Tianjin First Center Hospital, Tianjin 300192, China 4 Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding 071000, China * These authors have contributed equally to this work Correspondence to: Qiong Wang, email: lailwq@126.com Jinhuan Wang, email: wangjinhuanfch@126.com Keywords: miR-433-3p, CREB, glioma, carcinogenesis, chemosensitivity Received: June 16, 2016     Accepted: November 22, 2016     Published: December 03, 2016 ABSTRACT 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.