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-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.
Highlights
OSCC is one of the undertreated and understudied cancer types
The effects of miR-7 on the expression levels of these predicted targets were examined in a pair of TSCC cell lines (UM1 and UM2) that originated from a single TSCC patient [13]
MiRNAs contribute to a newly recognized level of fine-tuning regulation of gene expression. miRNA-7 has previously been characterized as a tumour-suppressor miRNA in several human cancers by targeting a number of key signalling molecules, including IRS1, IRS2, EGFR, RAF1 and PAK1 [10,11,12]
Summary
OSCC (squamous cell carcinoma of the oral cavity) is one of the undertreated and understudied cancer types. We were able to demonstrate that miR-7-mediated down-regulation of IGF1R attenuated the IGF1-induced activation of Akt (protein kinase B) and led to reduced cell proliferation and cell-cycle arrest, and to an increase in apoptosis rate. When UM1 cells were treated with miR-7 mimic, reductions in the protein levels of IGF1R, IRS2 and PAK1 were consistently observed.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
