MicroRNA-182 suppresses clear cell renal cell carcinoma migration and invasion by targeting IGF1R

被引:27
作者
Wang, X. [1 ,2 ]
Li, H. [2 ]
Cui, L. [2 ]
Feng, J. [3 ]
Fan, Q. [1 ]
机构
[1] Zhengzhou Univ, Affiliated Hosp 1, Dept Oncol, Zhengzhou 450052, Henan, Peoples R China
[2] Zhengzhou Univ, Affiliated Hosp 1, Dept Pathol, Zhengzhou 450052, Henan, Peoples R China
[3] Zhengzhou YIHE Hosp, Dept Resp Med, Zhengzhou 450047, Henan, Peoples R China
关键词
MicroRNA-182; clear cell renal cell carcinoma; migration and invasion; insulin-like growth factor 1 receptor; FACTOR-I RECEPTOR; GASTRIC-CANCER; METASTASIS; GROWTH; EXPRESSION; PROLIFERATION; CONTRIBUTES; MARKERS; MIR-182;
D O I
10.4149/neo_2016_508
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The purpose of our study was aimed to determine the functional role of microRNA (miR)-182 in clear cell renal cell carcinoma (ccRCC) and try to clarify its underlying molecular mechanism. Expression of miR-182 in both cancer and peripheral blood samples was analyzed by quantitative real-time PCR (qRT-PCR). Human RCC line Caki-1 cells were transfected with miR-182 mimic, miR-182 inhibitor, or negative controls, and then the cell viability, colony-formation ability, migration, and invasion assay were determined. Luciferase reporter assay, qRT-PCR and Western blotting were used to determine whether insulin-like growth factor 1 receptor (IGF1R) was a target of miR-182. Further, small interfering RNA (siRNA) against IGF1R was co-transfected with miR-182 inhibitor into cells, and then the effects on migration and invasion were assessed. MiR-182 was down-regulated in both cancer and blood samples compared to the matched non-tumor adjacent tissues and healthy volunteers, respectively (both P<0.05). Compared to the control group, cell viability, colony-forming ability, and numbers of migrated and invaded cells were significantly decreased by transfection with miR-182 mimic but were markedly increased by miR-182 inhibitor (all P < 0.05). Luciferase reporter assay confirmed that IGF1R was a target gene of miR-182, and IGF1R was negatively regulated by miR-182. Co-transfection of miR-182 inhibitor with si-IGF1R reversed the effect of miR-182 inhibitor on the migration and invasion of the cells. MiR-182 functions as an anti-oncogene in ccRCC, and miR-182-mediated inhibition of cell migration and invasion might be through directly targeting IGF1R.
引用
收藏
页码:717 / 725
页数:9
相关论文
共 36 条
[1]   The IGF system [J].
Annunziata, Marta ;
Granata, Riccarda ;
Ghigo, Ezio .
ACTA DIABETOLOGICA, 2011, 48 (01) :1-9
[2]   miRNA control of tumor cell invasion and metastasis [J].
Baranwal, Somesh ;
Alahari, Suresh K. .
INTERNATIONAL JOURNAL OF CANCER, 2010, 126 (06) :1283-1290
[3]   Differential expression profiling of microRNAs and their potential involvement in renal cell carcinoma pathogenesis [J].
Chow, Tsz-Fung F. ;
Youssef, Youssef M. ;
Lianidou, Evi ;
Romaschin, Alexander D. ;
Honey, R. John ;
Stewart, Robert ;
Pace, Kenneth T. ;
Yousef, George M. .
CLINICAL BIOCHEMISTRY, 2010, 43 (1-2) :150-158
[4]   Renal-cell carcinoma [J].
Cohen, HT ;
McGovern, FJ .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (23) :2477-2490
[5]   Recent developments in the treatment of renal cell carcinoma [J].
Dutcher, Janice P. .
THERAPEUTIC ADVANCES IN UROLOGY, 2013, 5 (06) :338-353
[6]   MicroRNAs and Metastasis: Little RNAs Go a Long Way [J].
Dykxhoorn, Derek M. .
CANCER RESEARCH, 2010, 70 (16) :6401-6406
[7]   MicroRNAs and Cancer: Introduction [J].
Garzon, Ramiro ;
Croce, Carlo M. .
SEMINARS IN ONCOLOGY, 2011, 38 (06) :721-723
[8]   Tumor suppressor role of miR-133a in gastric cancer by repressing IGF1R [J].
Gong, Yu ;
Ren, Jun ;
Liu, Kun ;
Tang, Li-Ming .
WORLD JOURNAL OF GASTROENTEROLOGY, 2015, 21 (10) :2949-2958
[9]  
Ha N. H., 2013, CANC TARGET DRUG DEL, P435, DOI [10.1007/978-1-4614-7876-8_17, DOI 10.1007/978-1-4614-7876-8_17]
[10]   Microarray analysis of microRNA expression in renal clear cell carcinoma [J].
Huang, Y. ;
Dai, Y. ;
Yang, J. ;
Chen, T. ;
Yin, Y. ;
Tang, M. ;
Hu, C. ;
Zhang, L. .
EJSO, 2009, 35 (10) :1119-1123