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

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posted on 03.12.2013 by Lu Juiang, Xiqiang Lui, Zujian Chen, Yi Jin, Caroline E. Heidbreder, Antonia Kolokythas, Anxun Wang, Yang Dai, Xiaofeng Zhou
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.

Funding

This work was supported in part by the National Institutes of Health Public Health Service [grant numbers K22DE014847, RO1CA139596 and RO3CA135992] and the Prevent Cancer Foundation (to X.Z.).

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Publisher Statement

The final version of record is available at http://www.biochemj.org/bj/default.htm

Publisher

Portland Press

Language

en_US

issn

0264-6021

Issue date

01/11/2010

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