Downregulated TIPE2 is associated with poor prognosis and promotes cell proliferation in non-small cell lung cancer

被引:41
作者
Li, Yuexia [1 ]
Li, Xiaohui [2 ]
Liu, Gang [1 ]
Sun, Rongqing [1 ]
Wang, Lirui [1 ]
Wang, Jing [3 ]
Wang, Hongmin [3 ]
机构
[1] Zhengzhou Univ, Affiliated Hosp 1, Intens Care Unit, Zhengzhou 450052, Henan, Peoples R China
[2] Henan Prov Peoples Hosp, Dept Cardiovasc Surg, Zhengzhou 450003, Henan, Peoples R China
[3] Zhengzhou Univ, Affiliated Hosp 1, Dept Resp Med, Zhengzhou 450052, Henan, Peoples R China
关键词
TIPE2; Non-small cell lung cancer; Tumor suppressor; Proliferation; Invasive; EPITHELIAL-MESENCHYMAL TRANSITION; TUMOR; METASTASIS; IMMUNITY; FAMILY;
D O I
10.1016/j.bbrc.2014.12.080
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The present study aims to investigate the expression pattern of TIPE2 protein and its clinical significance in human non-small cell lung cancer (NSCLC). We investigated the expression levels of TIPE2 in 96 NSCLC tumor samples by immunohistochemistry and then analyzed its clinical significance. Furthermore, the role of TIPE2 on the biological properties of the NSCLC cell line H1299 and A549 was experimentally tested in vitro and in vivo. We found that the expression level of TIPE2 was significantly higher in normal lung tissues compared with NSCLC tissues (P < 0.001), and TIPE2 downregulation was significantly correlated with advanced TNM stage (P = 0.006). TIPE2 expression was lower in lung cancer cell lines than normal bronchial cell line HBE. Transfection of TIPE2 plasmid was performed in H1299 and A549 cells. TIPE2 overexpression inhibited lung cancer cell proliferation, colony formation and cell invasive in vitro, and prevented lung tumor growth in vivo. In addition, TIPE2 transfection reduced the anti-apoptotic Bcl-XL protein and mesenchymal marker N-cadherin expression. Taken together, our results demonstrate that TIPE2 might serve as a tumor suppressor in NSCLC progression. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:43 / 49
页数:7
相关论文
共 19 条
[1]   Human tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 suppresses hepatocellular carcinoma metastasis through inhibiting Rac1 [J].
Cao, Xuelei ;
Zhang, Li ;
Shi, Yongyu ;
Sun, Yue ;
Dai, Shen ;
Guo, Chun ;
Zhu, Faliang ;
Wang, Qun ;
Wang, Jianing ;
Wang, Xiaoyan ;
Chen, Youhai H. ;
Zhang, Lining .
MOLECULAR CANCER, 2013, 12
[2]   Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy [J].
Czabotar, Peter E. ;
Lessene, Guillaume ;
Strasser, Andreas ;
Adams, Jerry M. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2014, 15 (01) :49-63
[3]   BCL-2 family members and the mitochondria in apoptosis [J].
Gross, A ;
McDonnell, JM ;
Korsmeyer, SJ .
GENES & DEVELOPMENT, 1999, 13 (15) :1899-1911
[4]   The Anti-inflammatory TIPE2 Is an Inhibitor of the Oncogenic Ras [J].
Gus-Brautbar, Yael ;
Johnson, Derek ;
Zhang, Li ;
Sun, Honghong ;
Wang, Peng ;
Zhang, Shirley ;
Zhang, Lining ;
Chen, Youhai H. .
MOLECULAR CELL, 2012, 45 (05) :610-618
[5]   Molecular requirements for epithelial-mesenchymal transition during tumor progression [J].
Huber, MA ;
Kraut, N ;
Beug, H .
CURRENT OPINION IN CELL BIOLOGY, 2005, 17 (05) :548-558
[6]  
JEMAL A, 2011, CA-CANCER J CLIN, V61, P69, DOI DOI 10.3322/CAAC.20107
[7]   The basics of epithelial-mesenchymal transition [J].
Kalluri, Raghu ;
Weinberg, Robert A. .
JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (06) :1420-1428
[8]   Down-regulation of TIPE2 mRNA expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus [J].
Li, Di ;
Song, Lijun ;
Fan, Yuchen ;
Li, Xia ;
Li, Yingjie ;
Chen, Jie ;
Zhu, Faliang ;
Guo, Chun ;
Shi, Yongyu ;
Zhang, Lining .
CLINICAL IMMUNOLOGY, 2009, 133 (03) :422-427
[9]   TRIM31 is downregulated in non-small cell lung cancer and serves as a potential tumor suppressor [J].
Li, Hui ;
Zhang, Yi ;
Zhang, Yue ;
Bai, Xue ;
Peng, Yang ;
He, Ping .
TUMOR BIOLOGY, 2014, 35 (06) :5747-5752
[10]   A novel inflammatory regulator TIPE2 inhibits TLR4-mediated development of colon cancer via caspase-8 [J].
Li, Xue-Mei ;
Su, Jing-Ran ;
Yan, Shi-Ping ;
Cheng, Zhao-Ling ;
Yang, Ting-Ting ;
Zhu, Qiang .
CANCER BIOMARKERS, 2014, 14 (04) :233-240