microRNA-5481 is involved in the migration and invasion of non-small cell lung cancer by targeting the AKT1 signaling pathway

被引:30
作者
Liu, Caihong [1 ]
Yang, Huan [1 ]
Xu, Zhijie [2 ]
Li, Dan [3 ]
Zhou, Meiyu [1 ]
Xiao, Kui [1 ]
Shi, Zhihui [1 ]
Zhu, Lanyan [1 ]
Yang, Lifang [2 ]
Zhou, Rui [1 ]
机构
[1] Cent S Univ, Xiangya Hosp 2, Dept Resp Med, Changsha, Hunan, Peoples R China
[2] Cent S Univ, Canc Res Inst, Changsha, Hunan, Peoples R China
[3] Hunan Univ, Coll Biol, Dept Life Sci, Changsha 410082, Hunan, Peoples R China
关键词
miR-5481; Migration; Invasion; AKT1; NSCLC; EXPRESSION; PROLIFERATION; METASTASIS; ACTIVATION; SUPPRESSOR; APOPTOSIS; SURVIVAL; GROWTH;
D O I
10.1007/s00432-014-1836-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose microRNAs (miRNAs) have been documented playing a critical role in cancer development and progression. In this study, we investigated the role of miR-5481 in non-small cell lung cancer (NSCLC) migration and invasion. Methods microRNAs microarray analysis was used to detect the differentially expressed miRNAs between various metastatic levels of NSCLC cells and further confirmed by real-time PCR analysis. To facilitate the delineation of the role of selected miR-5481 in NSCLC pathology, we detected its expression in 22 NSCLC tissues. Proliferation, apoptosis, invasion and metastasis effects of the miRNA were evaluated using MTT, flow cytometry, wound healing and invasion assay following transfection with mimics and inhibitors. Luciferase assay and Western blot analysis were performed to assess miR-5481 binding to AKT1 gene. AKT1 expression in the clinical tissues was evaluated using immunohistochemical staining. Results The results showed a negative relationship between miR-5481 expression and lymph node metastasis of NSCLC. Functional assays showed that over-expression of miR-5481 suppressed NSCLC cell migration and invasion. Luciferase assays confirmed that miR-5481 could directly bind to the 3' untranslated region of AKT1. Further data showed that the over-expression of AKT1 could rescue the effects of miR-5481 in NSCLC cells, and the miR-5481 expression was inversely correlated with AKT1 expression in NSCLC tissues. These results indicated that AKT1 was involved in miR-5481-induced suppression of NSCLC cell migration and invasion. Conclusion These results suggested that miR-5481 may play a causal role through AKT1 in NSCLC invasion and metastasis.
引用
收藏
页码:431 / 441
页数:11
相关论文
共 25 条
[1]   Understanding the role of tissue degrading enzymes and their inhibitors in development and disease [J].
Cawston, Tim E. ;
Wilson, Amy J. .
BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY, 2006, 20 (05) :983-1002
[2]   Decreased miRNA-148a is associated with lymph node metastasis and poor clinical outcomes and functions as a suppressor of tumor metastasis in non-small cell lung cancer [J].
Chen, Yong ;
Min, Lingfeng ;
Zhang, Xizhi ;
Hu, Suwei ;
Wang, Buhai ;
Liu, Wei ;
Wang, Rui ;
Gu, Xuewen ;
Shen, Weigan ;
Lv, Houning ;
Zou, Jing ;
Chen, Yuexiang ;
Xu, Xingxiang ;
Chen, Longbang .
ONCOLOGY REPORTS, 2013, 30 (04) :1832-1840
[3]   Platelet-type 12-lipoxygenase induces MMP9 expression and cellular invasion via activation of PI3K/Akt/NF-B [J].
Dilly, Ashok-Kumar ;
Ekambaram, Prasanna ;
Guo, Yande ;
Cai, Yinlong ;
Tucker, Stephanie C. ;
Fridman, Rafael ;
Kandouz, Mustapha ;
Honn, Kenneth V. .
INTERNATIONAL JOURNAL OF CANCER, 2013, 133 (08) :1784-1791
[4]   miR-93, miR-98, and miR-197 Regulate Expression of Tumor Suppressor Gene FUS1 [J].
Du, Liqin ;
Schageman, Jeoffrey J. ;
Subauste, Maria C. ;
Saber, Barbara ;
Hammond, Scott M. ;
Prudkin, Ludmila ;
Wistuba, Ignacio I. ;
Ji, Lin ;
Roth, Jack A. ;
Minna, John D. ;
Pertsemlidis, Alexander .
MOLECULAR CANCER RESEARCH, 2009, 7 (08) :1234-1243
[5]   Estimates of cancer incidence and mortality in Europe in 2008 [J].
Ferlay, J. ;
Parkin, D. M. ;
Steliarova-Foucher, E. .
EUROPEAN JOURNAL OF CANCER, 2010, 46 (04) :765-781
[6]   PI3K/Akt: getting it right matters [J].
Franke, T. F. .
ONCOGENE, 2008, 27 (50) :6473-6488
[7]   Control of cell proliferation pathways by microRNAs [J].
Jose Bueno, Maria ;
Perez de Castro, Ignacio ;
Malumbres, Marcos .
CELL CYCLE, 2008, 7 (20) :3143-3148
[8]   PI3K-Dependent GSK3β(Ser9)-Phosphorylation Is Implicated in the Intestinal Epithelial Cell Wound-Healing Response [J].
Karrasch, Thomas ;
Spaeth, Tanja ;
Allard, Brigitte ;
Jobin, Christian .
PLOS ONE, 2011, 6 (10)
[9]   miR-149 Inhibits Non-Small-Cell Lung Cancer Cells EMT by Targeting FOXM1 [J].
Ke, Yang ;
Zhao, Weiyong ;
Xiong, Jie ;
Cao, Rubo .
BIOCHEMISTRY RESEARCH INTERNATIONAL, 2013, 2013
[10]   Selective activation of Akt1 by mammalian target of rapamycin complex 2 regulates cancer cell migration, invasion, and metastasis [J].
Kim, E. K. ;
Yun, S. J. ;
Ha, J. M. ;
Kim, Y. W. ;
Jin, I. H. ;
Yun, J. ;
Shin, H. K. ;
Song, S. H. ;
Kim, J. H. ;
Lee, J. S. ;
Kim, C. D. ;
Bae, S. S. .
ONCOGENE, 2011, 30 (26) :2954-2963