HMGN5 blockade by siRNA enhances apoptosis, suppresses invasion and increases chemosensitivity to temozolomide in meningiomas

被引:14
作者
He, Jing [1 ]
Liu, Chaoyang [1 ]
Wang, Bin [1 ]
Li, Na [1 ]
Zuo, Guoqin [1 ]
Gao, Dewei [1 ]
机构
[1] Chinese Peoples Liberat Army Gen Hosp, Integrated Surg Dept South Bldg, Beijing 100853, Peoples R China
关键词
HMGN5; meningiomas; apoptosis; invasion; temozolomide; MATRIX METALLOPROTEINASE-2; BINDING-PROTEIN; FAMILY-MEMBERS; IN-VITRO; EXPRESSION; CELLS; PROLIFERATION; HETEROGENEITY; GLIOBLASTOMA; KNOCKDOWN;
D O I
10.3892/ijo.2015.3131
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The high-mobility group nucleosome-binding protein-5 (HMGN5) is frequently overexpressed in various malignant cancers. However, the potential correlation between HMGN5 and prognosis in patients with meningiomas remains unknown. In the present study, we explored the expression of HMGN5 in meningiomas with immunohistochemistry and correlated the results to the patient outcome. Potential effects of HMGN5 on tumor growth, apoptosis and invasion were also examined in representative cell lines (IOMM-Lee and CH157) by downregulating HMGN5 with RNA interference (siRNA). We demonstrate that there is a positive association between HMGN5 expression and meningioma histological grade. Statistical analysis reveals that lower HMGN5 expression predict lower meningioma recurrence. In addition, downregulation of HMGN5 inhibits IOMM-Lee and CH157 cell proliferation, enhances cell apoptosis and suppresses tumor invasion. Our results further revealed that HMGN5 inhibition decreased P-glycoprotein (MDR-1) expression without affecting multidrug resistance associated proteins 1 (MRP-1) expression to increase chemosensitivity to temozolomide (TMZ) of meningioma cells. Collectively, this study indicates that HMGN5 is a novel target for developing effective therapeutic strategies for malignant meningiomas.
引用
收藏
页码:1503 / 1511
页数:9
相关论文
共 28 条
[1]  
Akay C, 2004, CELL CYCLE, V3, P324
[2]  
Andersson U, 2004, CLIN NEUROPATHOL, V23, P21
[3]   Posttranslational modifications of Bcl2 family members - a potential therapeutic target for human malignancy [J].
Basu, A ;
DuBois, G ;
Haldar, S .
FRONTIERS IN BIOSCIENCE-LANDMARK, 2006, 11 :1508-1521
[4]   Temozolomide for treatment resistant recurrent meningioma [J].
Chamberlain, MC ;
Wei-Tsao, D ;
Groshen, S .
NEUROLOGY, 2004, 62 (07) :A473-A473
[5]   Contemporary Endovascular Embolotherapy for Meningioma [J].
Dubel, Gregory J. ;
Ahn, Sun Ho ;
Soares, Gregory M. .
SEMINARS IN INTERVENTIONAL RADIOLOGY, 2013, 30 (03) :263-277
[6]   Meningioma [J].
Fathi, Ali-Reza ;
Roelcke, Ulrich .
CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS, 2013, 13 (04)
[7]   Knockdown of the nucleosome binding protein 1 inhibits the growth and invasion of clear cell renal cell carcinoma cells in vitro and in vivo [J].
Ji, Shi-Qi ;
Yao, Lin ;
Zhang, Xiao-Yu ;
Li, Xue-Song ;
Zhou, Li-Qun .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2012, 31
[8]   Downregulation of the nucleosome-binding protein 1 (NSBP1) gene can inhibit the in vitro and in vivo proliferation of prostate cancer cells [J].
Jiang, Ning ;
Zhou, Li-Qun ;
Zhang, Xiao-Yu .
ASIAN JOURNAL OF ANDROLOGY, 2010, 12 (05) :709-717
[9]   Matrix Metalloproteinase-2 and -9 in Glioblastoma: A Trio of Old Drugs-Captopril, Disulfiram and Nelfinavir-Are Inhibitors with Potential as Adjunctive Treatments in Glioblastoma [J].
Kast, Richard E. ;
Halatsch, Marc-Eric .
ARCHIVES OF MEDICAL RESEARCH, 2012, 43 (03) :243-247
[10]   Effect of temozolomide on livin and caspase-3 in U251 glioma stem cells [J].
Li, Genhua ;
Zhang, Hao ;
Liu, Yang ;
Kong, Lingsheng ;
Guo, Qiang ;
Jin, Feng .
EXPERIMENTAL AND THERAPEUTIC MEDICINE, 2015, 9 (03) :744-750