Expression and function of miRNA in postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer

被引:98
作者
Wang, Xiao-Chun [1 ]
Du, Li-Qing [1 ]
Tian, Li-Li [2 ]
Wu, Hai-Liang [3 ]
Jiang, Xiao-Yan [4 ]
Zhang, Heng [1 ]
Li, De-Guan [1 ]
Wang, Yue-Ying [1 ]
Wu, Hong-Ying [1 ]
She, Yi [1 ]
Liu, Qing-fen [1 ]
Fan, Fei-Yue [1 ]
Meng, Ai-Min [1 ]
机构
[1] Chinese Acad Med Sci, Inst Radiat Med, Tianjin Key Lab Mol Nucl Med, Tianjin 300192, Peoples R China
[2] Beijing Ctr Dis Control & Prevent, Inst Infect & Endem Dis Prevent, Beijing 100013, Peoples R China
[3] Shandong Prov Chest Hosp, Dept Tumor Med, Jinan 250013, Peoples R China
[4] Chinese Ctr Dis Control & Prevent, Natl Inst Radiol Protect & Nucl Safety, Dept Policy & Stand Res, Beijing 100050, Peoples R China
基金
高等学校博士学科点专项科研基金; 中国国家自然科学基金;
关键词
miRNA; Radiotherapy sensitivity; Apoptosis; NSCLC; RADIATION-THERAPY; MICRORNA; PROFILES; GENE; CARCINOMA; GROWTH; RNA;
D O I
10.1016/j.lungcan.2010.07.014
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: To investigate the different miRNA expression profiles of postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer, explore their potential role and find some radiosensitivity markers. Materials and methods: Thirty non-small cell lung cancer patients who have been treated by postoperative radiotherapy were selected and were divided into radiotherapy sensitive group and resistant group according to overall survival and local or distant recurrence rate. Expression profile of miRNA in these two groups was detected by a microarray assay and the results were validated by quantitative RT-PCR and Northern blot. At the molecular level, the effect of one differently expressed miRNA (miR-126) on the growth and apoptosis of SK-MES-1 cells induced by irradiation was examined. Results: Comparing with resistant patients, five miRNAs (miRNA-126, miRNA-let-7a, miRNA-495, miRNA-451 and miRNA-128b) were significantly upregulated and seven miRNAs (miRNA-130a, miRNA-106b, miRNA-19b, miRNA-22, miRNA-15b, miRNA-17-5p and miRNA-21) were greatly downregulated in radiotherapy sensitive group. Overexpression of miRNA-126 inhibited the growth of SK-MES-1 cells and promoted its apoptosis induced by irradiation. The expression level of p-Akt decreased in miRNA-126 overexpression group. After treating with phosphoinositidy1-3 kinase (PI3K) constitutively activator (IGF-1) and inhibitor (LY294002), miRNA-126 overexpression had no significant effects on the apoptosis of SK-MES-1 cells. Conclusion: We found 12 differently expressed miRNAs in the radiotherapy sensitive and resistant non-small cell lung cancer samples. Moreover, our results showed miRNA-126 promoted non-small cell lung cancer cells apoptosis induced by irradiation through the PI3K-Akt pathway. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:92 / 99
页数:8
相关论文
共 29 条
[1]  
Ahmed Farid E., 2009, Cancer Genomics & Proteomics, V6, P109
[2]   Chemotherapy and radiotherapy in the treatment of resectable non-small-cell lung cancer [J].
Bernstein, ED ;
Herbert, SM ;
Hanna, NH .
ANNALS OF SURGICAL ONCOLOGY, 2006, 13 (03) :291-301
[3]   A comparison of normalization methods for high density oligonucleotide array data based on variance and bias [J].
Bolstad, BM ;
Irizarry, RA ;
Åstrand, M ;
Speed, TP .
BIOINFORMATICS, 2003, 19 (02) :185-193
[4]   The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function [J].
Brueckner, Bodo ;
Stresemann, Carlo ;
Kuner, Ruprecht ;
Mund, Cora ;
Musch, Tanja ;
Meister, Michael ;
Sueltmann, Holger ;
Lyko, Frank .
CANCER RESEARCH, 2007, 67 (04) :1419-1423
[5]   Extensive modulation of a set of microRNAs in primary glioblastoma [J].
Ciafrè, SA ;
Galardi, S ;
Mangiola, A ;
Ferracin, M ;
Liu, CG ;
Sabatino, G ;
Negrini, M ;
Maira, G ;
Croce, CM ;
Farace, MG .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 334 (04) :1351-1358
[6]   Estrogen Protects against Radiation-Induced Cataractogenesis [J].
Dynlacht, Joseph R. ;
Valluri, Shallaja ;
Lopez, Jennifer ;
Greer, Falon ;
DesRosiers, Colleen ;
Caperell-Grant, Andrea ;
Mendonca, Marc S. ;
Bigsby, Robert M. .
RADIATION RESEARCH, 2008, 170 (06) :758-764
[7]   Detection of let-7a microRNA by real-time PCR in colorectal cancer:: a single-centre experience from China [J].
Fang, W. ;
Lin, C. ;
Zhang, H. ;
Qian, J. ;
Zhong, L. ;
Xu, N. .
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH, 2007, 35 (05) :716-723
[8]   MEAN INACTIVATION DOSE - A USEFUL CONCEPT FOR INTERCOMPARISON OF HUMAN CELL-SURVIVAL CURVES [J].
FERTIL, B ;
DERTINGER, H ;
COURDI, A ;
MALAISE, EP .
RADIATION RESEARCH, 1984, 99 (01) :73-84
[9]   In situ synthesis of oligonucleotide microarrays [J].
Gao, XL ;
Gulari, E ;
Zhou, XC .
BIOPOLYMERS, 2004, 73 (05) :579-596
[10]   The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers [J].
Guo, Chunguang ;
Sah, Jerome F. ;
Beard, Lydia ;
Willson, James K. V. ;
Markowitz, Sanford D. ;
Guda, Kishore .
GENES CHROMOSOMES & CANCER, 2008, 47 (11) :939-946