Knockdown of astrocyte elevated gene-1 inhibited cell growth and induced apoptosis and suppressed invasion in ovarian cancer cells

被引:18
作者
Wang, Jiewen [1 ]
Chen, Xiaodong [2 ]
Tong, Maoqing [3 ]
机构
[1] Bengbu Med Coll, Affiliated Hosp 2, Dept Gynecol & Obstet, Bengbu, Anhui, Peoples R China
[2] Fifth Hosp Bengbu, Dept Liver Dis, Bengbu, Anhui, Peoples R China
[3] Ningbo Univ, Sch Med, Affiliated Ningbo Hosp 1, Dept Cardiol, Ningbo, Zhejiang, Peoples R China
关键词
AEG-1; Ovarian cancer; Proliferation; Apoptosis; Invasion: pAkt; LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; AEG-1; EXPRESSION; DOWN-REGULATION; CLINICAL-SIGNIFICANCE; TUMOR PROGRESSION; C-MET; OVEREXPRESSION; PATHWAY; METASTASIS;
D O I
10.1016/j.gene.2017.03.024
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Emerging evidence has demonstrated that AEG-1 (astrocyte elevated gene-1) plays a pivotal oncogenic role in tumorigenesis. However, the molecular mechanism by which AEG-1 exerts its oncogenic function is elusive in ovarian cancer. To explore the role and molecular insight on AEG-1-mediated tumorigenesis in ovarian cancer, multiple approaches are performed including MTT assay, flow cytometry for apoptosis and cell cycle assay, gene transfection, real-time RT-PCR, Western blotting, and Transwell assay. Our MTT assay showed that knockdown of AEG-1 by its siRNA significantly inhibited cell growth in ovarian cancer cells. Moreover, AEG-1 siRNA treatment induced G(0)/G(1) cell cycle arrest and triggered cell apoptosis in ovarian cancer cells. Notably, inhibition of AEG-1 suppressed cell migration and invasion in ovarian cancer cells. Intriguingly, we identified that knockdown of AEG-1 remarkably inhibited the activation of Akt pathway. Our results also validated that knockdown of AEG-1 inhibited the expression of MMP-2 and VEGF, which could lead to inhibition of cell migration and invasion. These data suggest that AEG-1 could be a potential therapeutic target for the treatment of ovarian cancer. (C) 2017 Elsevier B.V. All rights reserved.
引用
收藏
页码:8 / 15
页数:8
相关论文
共 55 条
[1]   Specific immunotherapy in ovarian cancer: a systematic review [J].
Alipour, Soroush ;
Zoghi, Samaneh ;
Khalili, Nastaran ;
Hirbod-Mobarakeh, Armin ;
Emens, Leisha A. ;
Rezaei, Nima .
IMMUNOTHERAPY, 2016, 8 (10) :1193-1204
[2]   Current mechanistic insights into the roles of matrix metalloproteinases in tumour invasion and metastasis [J].
Brown, Gordon T. ;
Murray, Graeme I. .
JOURNAL OF PATHOLOGY, 2015, 237 (03) :273-281
[3]   Targeting matrix metalloproteinases in cancer: Bringing new life to old ideas [J].
Cathcart, Jillian ;
Pulkoski-Gross, Ashleigh ;
Cao, Jian .
GENES & DISEASES, 2015, 2 (01) :26-34
[4]   Lentivirus-Mediated Knockdown of Astrocyte Elevated Gene-1 Inhibits Growth and Induces Apoptosis through MAPK Pathways in Human Retinoblastoma Cells [J].
Chang, Ying ;
Li, Bin ;
Xu, Xiaolin ;
Shen, Ling ;
Bai, Haixia ;
Gao, Fei ;
Zhang, Zhibao ;
Jonas, Jost B. .
PLOS ONE, 2016, 11 (02)
[5]   Astrocyte elevated gene-1 (AEG-1) functions as an oncogene and regulates angiogenesis [J].
Emdad, Luni ;
Lee, Seok-Geun ;
Su, Zhao Zhong ;
Jeon, Hyun Yong ;
Boukerche, Habib ;
Sarkar, Devanand ;
Fisher, Paul B. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (50) :21300-21305
[6]   PI3K and cancer: lessons, challenges and opportunities [J].
Fruman, David A. ;
Rommel, Christian .
NATURE REVIEWS DRUG DISCOVERY, 2014, 13 (02) :140-156
[7]   The Expression of Tumor-Derived and Stromal-Derived Matrix Metalloproteinase 2 Predicted Prognosis of Ovarian Cancer [J].
Fu, Ziyi ;
Xu, Sujuan ;
Xu, Ye ;
Ma, Jiehua ;
Li, Jingyun ;
Xu, Pengfei .
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 2015, 25 (03) :356-362
[8]   miR-137 suppresses cell growth in ovarian cancer by targeting AEG-1 [J].
Guo, Jinling ;
Xia, Bairong ;
Meng, Fanling ;
Lou, Ge .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2013, 441 (02) :357-363
[9]   Astrocyte Elevated Gene-1 Interacts with Akt Isoform 2 to Control Glioma Growth, Survival, and Pathogenesis [J].
Hu, Bin ;
Emdad, Luni ;
Bacolod, Manny D. ;
Kegelman, Timothy P. ;
Shen, Xue-Ning ;
Alzubi, Mohammad A. ;
Das, Swadesh K. ;
Sarkar, Devanand ;
Fisher, Paul B. .
CANCER RESEARCH, 2014, 74 (24) :7321-7332
[10]   AEG-1 Is a Target of Perifosine and Is Over-Expressed in Gastric Dysplasia and Cancers [J].
Huang, Wenbin ;
Yang, Li ;
Liang, Song ;
Liu, Dongxiao ;
Chen, Xi ;
Ma, Zhuo ;
Zhai, Sulan ;
Li, Ping ;
Wang, Xuerong .
DIGESTIVE DISEASES AND SCIENCES, 2013, 58 (10) :2873-2880