Abstract

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.

Keywords

Insulin-like growth factor 1 receptorProtein kinase BmicroRNACell growthBiologyGene knockdownEctopic expressionCancer researchInsulin-like growth factorGrowth factorTransfectionGrowth factor receptorCell cycleCell cultureCell biologySignal transductionCellReceptorGeneBiochemistryGenetics

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Publication Info

Year
2010
Type
article
Volume
432
Issue
1
Pages
199-207
Citations
202
Access
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Lu Jiang, Xiqiang Liu, Zujian Chen et al. (2010). MicroRNA-7 targets IGF1R (insulin-like growth factor 1 receptor) in tongue squamous cell carcinoma cells. Biochemical Journal , 432 (1) , 199-207. https://doi.org/10.1042/bj20100859

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DOI
10.1042/bj20100859