MicroRNA-206 Inhibited the Progression of Glioblastoma Through BCL-2
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MicroRNA-206 Inhibited the Progression of Glioblastoma Through BCL-2 Wenjiong Hao 1,2 & Wei Luo 3 & Mangmang Bai 2 & Jian Li 2 & Xiaobin Bai 1 & Jie Guo 2 & Jinsong Wu 4 & Maode Wang 1
Received: 3 July 2016 / Accepted: 17 August 2016 # Springer Science+Business Media New York 2016
Abstract Gliomas are the most common type of brain tumor and have a poor prognosis. MicroRNAs (miRNAs) are a class of small, endogenous, and non-coding RNAs that play crucial roles in cell proliferation, survival, and invasion. Deregulated expression of miR-206 has been investigated in many cancers. However, the role of miR-206 in glioblastoma is still unclear. In the present study, we found that the expression of miR-206 was decreased in cancer tissues compared with normal tissues. However, the expression level of BCL-2 was higher in cancer tissues than that in normal tissues (all p < 0.001). Statistically, the expression level of BCL-2 was inversely correlated with the miR-206. In addition, the overall survival of glioblastoma patients with lower miR-206 expression was significantly shorter than those with high miR-206 expression (p < 0.001). Besides, the expression of miR-206 was also decreased in U87 and U251 cells. In vitro assays showed that ectopic miR-206 expression affected the proliferation, cell cycle, and invasion in U87 and U251 cells. Importantly, we identified BCL-2 as a direct target of miR-206 in U87 and U251 cells using luciferase assay. Overexpression of BCL-2
* Maode Wang [email protected] 1
Department of Neurosurgery, The First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710061, People’s Republic of China
2
Department of Neurosurgery, Affiliated Hospital, Medical College of Yan’an University, Yan’an City, Shaanxi 716000, People’s Republic of China
3
Department of Neurosurgery, The Affiliated Hospital of Shaanxi Traditional Chinese Medicine University, Xianyang 712000, People’s Republic of China
4
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China
partially attenuated the miR-206-mediated cell proliferation. In vivo, overexpression of miR-206 suppressed the progression of glioblastoma cells using mice xenograft model. In conclusion, this study suggested that miR-206 could act as a tumor suppressor gene through inhibiting BCL-2 in the development of glioblastoma. Keywords miR-206 . Glioblastoma . BCL-2 . Suppressor
Introduction Glioblastoma (GBM) is the most common form of primary malignant brain tumors, and the 5-year survival rate is less than 3 % (Zhao et al. 2016; Magaña-Maldonado et al. 2016; Bradshaw et al. 2016). Glioblastoma is characterized by malignant infiltration, invasiveness, and growth (Smith et al. 2016; Binder et al. 2015; Katakowski and Chopp, 2016; Krishna Priya et al. 2016; Khosla, 2016). Despite the combined treatment with chemotherapy, radiotherapy, and surgery, the overall survival of glioblastoma patients is just about 2 years. So, it is essential to identify novel effective targets to inhibit the d
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