MicroRNA-7 targets IGF1R (insulin-like growth factor 1 receptor) in tongue squamous cell carcinoma cells

被引:187
作者
Jiang, Lu [1 ]
Liu, Xiqiang [1 ]
Chen, Zujian [1 ]
Jin, Yi [1 ]
Heidbreder, Caroline E. [1 ]
Kolokythas, Antonia [2 ,3 ]
Wang, Anxun [1 ,4 ]
Dai, Yang [5 ]
Zhou, Xiaofeng [1 ,3 ]
机构
[1] Univ Illinois, Coll Dent, Ctr Mol Biol Oral Dis, Chicago, IL 60612 USA
[2] Univ Illinois, Coll Dent, Dept Oral & Maxillofacial Surg, Chicago, IL 60612 USA
[3] Univ Illinois, UIC Canc Ctr, Grad Coll, Chicago, IL 60612 USA
[4] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Oral & Maxillofacial Surg, Guangzhou 510275, Guangdong, Peoples R China
[5] Univ Illinois, Coll Engn, Dept Bioengn, Chicago, IL 60607 USA
基金
美国国家卫生研究院;
关键词
Akt (protein kinase B); insulin-like growth factor 1 receptor (IGF1R); microRNA-7 (miR-7); proliferation; tongue squamous cell carcinoma (TSCC); tumour suppressor; DISMUTASE; 2; SOD2; CANCER STATISTICS; GENE-EXPRESSION; IDENTIFICATION; INVASION; PATHWAY;
D O I
10.1042/BJ20100859
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
miR-7 (microRNA-7) has been characterized as a tumour suppressor in several human cancers. It targets a number of proto-oncogenes that contribute to cell proliferation and survival. However, the mechanism(s) by which miR-7 suppresses tumorigenesis in TSCC (tongue squamous cell carcinoma) is unknown. The present bioinformatics analysis revealed that IGF1R (insulin-like growth factor 1 receptor) mRNA is a potential target for miR-7. Ectopic transfection of miR-7 led to a significant reduction in IGF1R at both the mRNA and protein levels in TSCC cells. Knockdown of miR-7 in TSCC cells enhanced IGF1R expression. Direct targeting of miR-7 to three candidate binding sequences located in the 3'-untranslated region of IGF1R mRNA was confirmed using luciferase-reporter-gene assays. The miR-7-mediated down-regulation of IGF1R expression attenuated the IGF1 (insulin-like growth factor 1)-induced activation of Akt (protein kinase B) in TSCC cell lines, which in turn resulted in a reduction in cell proliferation and cell-cycle arrest, and an enhanced apoptotic rate. Taken together, the present results demonstrated that miR-7 regulates the IGF1R/Akt signalling pathway by post-transcriptional regulation of IGF1R. Our results indicate that miR-7 plays an important role in TSCC and may serve as a novel therapeutic target for TSCC patients.
引用
收藏
页码:199 / 205
页数:7
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