miR-494-3p Regulates Cellular Proliferation, Invasion, Migration, and Apoptosis by PTEN/AKT Signaling in Human Glioblastoma Cells

被引:102
作者
Li, Xue-tao [1 ,2 ]
Wang, Hang-zhou [3 ]
Wu, Zhi-wu [1 ,2 ]
Yang, Tian-quan [1 ,2 ]
Zhao, Zhao-hui [1 ,2 ]
Chen, Gui-lin [1 ,2 ]
Xie, Xue-shun [1 ,2 ]
Li, Bin [1 ,2 ]
Wei, Yong-xin [1 ,2 ]
Huang, Yu-lun [1 ,2 ]
Zhou, You-xin [1 ,2 ]
Du, Zi-wei [1 ,2 ]
机构
[1] Soochow Univ, Dept Neurosurg, Suzhou 215006, Jiangsu, Peoples R China
[2] Soochow Univ, Brain & Nerve Res Lab, Affiliated Hosp 1, Suzhou 215006, Jiangsu, Peoples R China
[3] Soochow Univ, Dept Neurosurg, Childrens Hosp Affiliated, Suzhou 215006, Jiangsu, Peoples R China
基金
美国国家科学基金会;
关键词
Glioma; MicroRNA; Migration; Apoptosis; PTEN; HUMAN GLIOMA-CELLS; GENE-MUTATIONS; EXPRESSION; ACTIVATION; GROWTH; CANCER; MICRORNA-494; SURVIVAL; PATHWAY; BREAST;
D O I
10.1007/s10571-015-0163-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Malignant gliomas are the most common primary brain tumors, and the molecular mechanisms involving their progression and recurrence are still largely unclear. Substantial data indicate that the oncogene miR-494-3p is significantly elevated in gliomas, but the molecular functions of miR-494-3p in gliomagenesis are largely unknown. The present study aimed to explore the role of miR-494-3p and its molecular mechanism in human brain gliomas, malignant glioma cell lines, and cancer stem-like cells. The expression level of miR-494-3p in 48 human glioma issues and 8 normal brain tissues was determined using stem-loop real-time polymerase chain reaction (PCR). To study the function of miR-494-3p inhibitor in glioma cells, the miR-494-3p inhibitor lentivirus was used to transfect glioma cells. Transwell invasion system was used to estimate the effects of miR-494-3p inhibitor on the invasiveness of glioma cells. A mouse model was used to test the effect of miR-494-3p inhibitor on glioma proliferation and invasion in vivo. Results showed that the expression of miR-494-3p in human brain glioma tissues was higher than in normal brain tissues. Downregulated expression of miR-494-3p can inhibit the invasion and proliferation and promote apoptosis in glioma cells. Quantitative reverse transcription PCR and Western blotting analysis revealed that the expression of PTEN was increased after downexpression of miR-494-3p in glioma cells (U87 and U251). miR-494-3p inhibitor could prevent migration, invasion, proliferation, and promote apotosis in gliomas through PTEN/AKT pathway. Therefore, the study results have shown that miR-494-3p may act as a therapeutic target in gliomas.
引用
收藏
页码:679 / 687
页数:9
相关论文
共 31 条
[11]   PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer [J].
Li, J ;
Yen, C ;
Liaw, D ;
Podsypanina, K ;
Bose, S ;
Wang, SI ;
Puc, J ;
Miliaresis, C ;
Rodgers, L ;
McCombie, R ;
Bigner, SH ;
Giovanella, BC ;
Ittmann, M ;
Tycko, B ;
Hibshoosh, H ;
Wigler, MH ;
Parsons, R .
SCIENCE, 1997, 275 (5308) :1943-1947
[12]   Down-regulation of MicroRNA-494 via Loss of SMAD4 Increases FOXM1 and β-Catenin Signaling in Pancreatic Ductal Adenocarcinoma Cells [J].
Li, Lei ;
Li, Zhaoshen ;
Kong, Xiangyu ;
Xie, Dacheng ;
Jia, Zhiliang ;
Jiang, Weihua ;
Cui, Jiujie ;
Du, Yiqi ;
Wei, Daoyan ;
Huang, Suyun ;
Xie, Keping .
GASTROENTEROLOGY, 2014, 147 (02) :485-+
[13]   Overexpressed miR-494 down-regulates PTEN gene expression in cells transformed by anti-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide [J].
Liu, Linhua ;
Jiang, Yiguo ;
Zhang, Hongyu ;
Greenlee, Anne R. ;
Han, Zhiyuan .
LIFE SCIENCES, 2010, 86 (5-6) :192-198
[14]   MicroRNA-494 Is Required for the Accumulation and Functions of Tumor-Expanded Myeloid-Derived Suppressor Cells via Targeting of PTEN [J].
Liu, Yang ;
Lai, Lihua ;
Chen, Qingyun ;
Song, Yinjing ;
Xu, Sheng ;
Ma, Feng ;
Wang, Xiaojian ;
Wang, Jianli ;
Yu, Hai ;
Cao, Xuetao ;
Wang, Qingqing .
JOURNAL OF IMMUNOLOGY, 2012, 188 (11) :5500-5510
[15]   Insulin growth factor-binding protein 2 is a candidate biomarker for PTEN status and PI3K-Akt pathway activation in glioblastoma and prostate cancer [J].
Mehrian-Shai, R. ;
Chen, C. D. ;
Shi, T. ;
Horvath, S. ;
Nelson, S. F. ;
Reichardt, J. K. V. ;
Sawyers, C. L. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (13) :5563-5568
[16]   PTEN promoter methylation and activation of the PI3K/Akt/mTOR pathway in pediatric gliomas and influence on clinical outcome [J].
Mueller, Sabine ;
Phillips, Joanna ;
Onar-Thomas, Arzu ;
Romero, Eloy ;
Zheng, Shichun ;
Wiencke, John K. ;
McBride, Sean M. ;
Cowdrey, Cynthia ;
Prados, Michael D. ;
Weiss, William A. ;
Berger, Mitchel S. ;
Gupta, Nalin ;
Haas-Kogan, Daphne A. .
NEURO-ONCOLOGY, 2012, 14 (09) :1146-1152
[17]  
Rasheed BKA, 1997, CANCER RES, V57, P4187
[18]   Pathology and molecular genetics of astrocytic gliomas [J].
Reifenberger, G ;
Collins, VP .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2004, 82 (10) :656-670
[19]   MicroRNA-21 inhibitor sensitizes human glioblastoma cells U251 (PTEN-mutant) and LN229 (PTEN-wild type) to taxol [J].
Ren, Yu ;
Zhou, Xuan ;
Mei, Mei ;
Yuan, Xu-Bo ;
Han, Lei ;
Wang, Guang-Xiu ;
Jia, Zhi-Fan ;
Xu, Peng ;
Pu, Pei-Yu ;
Kang, Chun-Sheng .
BMC CANCER, 2010, 10
[20]   Autocrine signaling through Ras regulates cell survival activity in human glioma cells: Potential cross-talk between Ras and the phosphatidylinositol 3-kinase-Akt pathway [J].
Sakata, K ;
Kato, S ;
Fox, JC ;
Shigemori, M ;
Morimatsu, M .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2002, 61 (11) :975-983