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-7mediated 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.
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Research Article|
October 25 2010
MicroRNA-7 targets IGF1R (insulin-like growth factor 1 receptor) in tongue squamous cell carcinoma cells
Lu Jiang;
Lu Jiang
*Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Chicago, IL 60612, U.S.A.
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Xiqiang Liu;
Xiqiang Liu
*Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Chicago, IL 60612, U.S.A.
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Zujian Chen;
Zujian Chen
*Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Chicago, IL 60612, U.S.A.
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Yi Jin;
Yi Jin
*Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Chicago, IL 60612, U.S.A.
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Caroline E. Heidbreder;
Caroline E. Heidbreder
*Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Chicago, IL 60612, U.S.A.
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Antonia Kolokythas;
Antonia Kolokythas
†Department of Oral and Maxillofacial Surgery, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Chicago, IL 60612, U.S.A.
‡Graduate College, UIC Cancer Center, University of Illinois at Chicago, 914 South Wood Street, Chicago, IL 60612, U.S.A.
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Anxun Wang;
Anxun Wang
*Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Chicago, IL 60612, U.S.A.
§Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Road II, Guangzhou, China
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Yang Dai;
Yang Dai
∥Department of Bioengineering, College of Engineering, University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607, U.S.A.
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Xiaofeng Zhou
Xiaofeng Zhou
1
*Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Chicago, IL 60612, U.S.A.
‡Graduate College, UIC Cancer Center, University of Illinois at Chicago, 914 South Wood Street, Chicago, IL 60612, U.S.A.
1To whom correspondence should be addressed (email xfzhou@uic.edu).
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Publisher: Portland Press Ltd
Received:
June 09 2010
Revision Received:
September 01 2010
Accepted:
September 07 2010
Accepted Manuscript online:
September 07 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 432 (1): 199–207.
Article history
Received:
June 09 2010
Revision Received:
September 01 2010
Accepted:
September 07 2010
Accepted Manuscript online:
September 07 2010
Citation
Lu Jiang, Xiqiang Liu, Zujian Chen, Yi Jin, Caroline E. Heidbreder, Antonia Kolokythas, Anxun Wang, Yang Dai, Xiaofeng Zhou; MicroRNA-7 targets IGF1R (insulin-like growth factor 1 receptor) in tongue squamous cell carcinoma cells. Biochem J 15 November 2010; 432 (1): 199–207. doi: https://doi.org/10.1042/BJ20100859
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