Two lung development-related microRNAs, miR-134 and miR-187, are differentially expressed in lung tumors

被引:30
作者
Azad, F. Mirzadeh [1 ]
Naeli, P. [1 ]
Malakootian, M. [2 ]
Baradaran, A. [3 ]
Tavallaei, M. [4 ]
Ghanei, M. [5 ]
Mowla, S. J. [1 ]
机构
[1] Tarbiat Modares Univ, Fac Biol Sci, Dept Mol Genet, Tehran, Iran
[2] Iran Univ Med Sci, Rajaie Cardiovasc Med & Res Ctr, Tehran, Iran
[3] Isfahan Univ Med Sci, Alzahra Hosp, Dept Pathol, Esfahan, Iran
[4] Baqiatallah Univ Med Sci, Genet Res Ctr, Tehran, Iran
[5] Baqiyatallah Univ Med Sci, Chem Injuries Res Ctr, Tehran, Iran
关键词
Lung cancer; Tumor marker; Development related miRNAs; miR-134; miR-187; Biomarkers; MESENCHYMAL TRANSITION; CELL-PROLIFERATION; CANCER; WWOX; PROGRESSION; GROWTH; B7-H3; PHOSPHORYLATION; ASSOCIATION; BIOMARKERS;
D O I
10.1016/j.gene.2015.11.040
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Introduction: MicroRNAs (miRNAs) are involved in various cellular events needed for embryonic development and tumorigenesis. As some of the development-specific gene expression patterns could be observed in cancers, we speculated that the expression pattern of lung development-specific miRNAs miR-134 and miR-187 might be altered in lung tumor samples. Lung cancer is the first cause of cancer related deaths worldwide, mostly due to its late diagnosis. Therefore, finding a reliable diagnostic tumor marker, based on molecular profile of tumorigenesis, would be critical in lowering lung cancer mortality. Methods: We employed a real-time RT-PCR approach to evaluate the expression alteration of two lung development-related miRNAs in lung tumor tissues. The suitability of miRs expression alterations as lung tumor biomarkers was tested by receiver operating characteristic (ROC) curve analysis. The effect of miR-187 overexpression on a lung carcinoma cell cycle was assessed using flow cytometry analysis. Results: Our data revealed a significant upregulation (7.8 times, p < 0.02) of miR-134 in lung tumors. However, its expression level failed to discriminate different tumor types and grades of malignancies from each other. Moreover, the ROC curves analysis did not give it a good score as a reliable biomarker (AUC = 0.522, P = 0.729). In contrast, miR-187 showed a significant down-regulation (P = 0.008) in lung tumors. Similarly, its expression level failed to differentiate different tumor types or grades of malignancies. Nevertheless, ROC curve analysis gave it an AUC score of 0.669 (P = 0.012), which suggests its suitability as a potential biomarker for lung cancer. Furthermore, ectopic expression of miR-187 in A549 cells caused a cell cycle arrest in GI phase (P = 0.013). Conclusion: Altogether, our data demonstrated an altered expression of two development-related miRNAs namely miR-134 and miR-187 in lung tumors for the first time. Moreover we have shown that miR-134 and miR-187 expression alternation were in accordance with their approved regulatory roles, therefore these miRNAs could serve as new biomarkers with potential usefulness in lung cancer diagnosis and treatments. In addition, miR-187 expression in tumor cells could perturb cell cycle which supported its possible role as tumor suppressor. (C) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码:221 / 226
页数:6
相关论文
共 42 条
[1]   Functional association between Wwox tumor suppressor protein and p73, a p53 homolog [J].
Aqeilan, RI ;
Pekarsky, Y ;
Herrero, JJ ;
Palamarchuk, A ;
Letofsky, J ;
Druck, T ;
Trapasso, F ;
Han, SY ;
Melino, G ;
Huebner, K ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (13) :4401-4406
[2]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[3]   MicroRNA-127 modulates fetal lung development [J].
Bhaskaran, Manoj ;
Wang, Yang ;
Zhang, Honghao ;
Weng, Tingting ;
Baviskar, Pradyumna ;
Guo, Yujie ;
Gou, Deming ;
Liu, Lin .
PHYSIOLOGICAL GENOMICS, 2009, 37 (03) :268-278
[4]   Molecular profiling of mouse lung tumors: association with tumor progression, lung development, and human lung adenocarcinomas [J].
Bonner, AE ;
Lemon, WJ ;
Devereux, TR ;
Lubet, RA ;
You, M .
ONCOGENE, 2004, 23 (05) :1166-1176
[5]   Early detection of lung cancer: role of biomarkers [J].
Brambilla, C ;
Fievet, F ;
Jeanmart, M ;
de Fraipont, F ;
Lantuejoul, S ;
Frappat, V ;
Ferretti, G ;
Brichon, PY ;
Moro-Sibilot, D .
EUROPEAN RESPIRATORY JOURNAL, 2003, 21 :36S-44S
[6]   bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila [J].
Brennecke, J ;
Hipfner, DR ;
Stark, A ;
Russell, RB ;
Cohen, SM .
CELL, 2003, 113 (01) :25-36
[7]   Regulation of ovarian cancer progression by microRNA-187 through targeting Disabled homolog-2 [J].
Chao, A. ;
Lin, C-Y ;
Lee, Y-S ;
Tsai, C-L ;
Wei, P-C ;
Hsueh, S. ;
Wu, T-I ;
Tsai, C-N ;
Wang, C-J ;
Chao, A-S ;
Wang, T-H ;
Lai, C-H .
ONCOGENE, 2012, 31 (06) :764-775
[8]   Induced expression of B7-H3 on the lung cancer cells and macrophages suppresses T-cell mediating anti-tumor immune response [J].
Chen, Cheng ;
Shen, Yu ;
Qu, Qiu-Xia ;
Chen, Xu-Qin ;
Zhang, Xue-Guang ;
Huang, Jian-An .
EXPERIMENTAL CELL RESEARCH, 2013, 319 (01) :96-102
[9]   Causes and consequences of microRNA dysregulation in cancer [J].
Croce, Carlo M. .
NATURE REVIEWS GENETICS, 2009, 10 (10) :704-714
[10]   Non-Small Cell Lung Cancer [J].
Ettinger, David S. ;
Akerley, Wallace ;
Borghaei, Hossein ;
Chang, Andrew C. ;
Cheney, Richard T. ;
Chirieac, Lucian R. ;
D'Amico, Thomas A. ;
Demmy, Todd L. ;
Ganti, Apar Kishor P. ;
Govindan, Ramaswamy ;
Grannis, Frederic W., Jr. ;
Horn, Leora ;
Jahan, Thierry M. ;
Jahanzeb, Mohammad ;
Kessinger, Anne ;
Komaki, Ritsuko ;
Kong, Feng-Ming ;
Kris, Mark G. ;
Krug, Lee M. ;
Lennes, Inga T. ;
Loo, Billy W., Jr. ;
Martins, Renato ;
O'Malley, Janis ;
Osarogiagbon, Raymond U. ;
Otterson, Gregory A. ;
Patel, Jyoti D. ;
Pinder-Schenck, Mary C. ;
Pisters, Katherine M. ;
Reckamp, Karen ;
Riely, Gregory J. ;
Rohren, Eric ;
Swanson, Scott J. ;
Wood, Douglas E. ;
Yang, Stephen C. ;
Hughes, Miranda ;
Gregory, Kristina M. .
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK, 2012, 10 (10) :1236-1271