Abstract
MicroRNAs are important regulators of gene expression and have been suggested to play a key role in tumorigenesis. In this study, we show that miR-145 is significantly downregulated in glioma cell lines compared to normal brain tissue and negatively regulates tumorigenesis. Restoration of miR-145 in glioma cells significantly reduced in vitro proliferation, migration and invasion. Also, overexpression of miR-145 reduced ADAM17 and EGFR expression. In addition, we tested the hypothesis that the miR-145-mediated suppression of cell proliferation, migration and invasion is, at least in part, due to silencing of ADAM17 and EGFR gene expression. Using luciferase reporters carrying the 3′-untranslated region of ADAM17 combined with western blotting, we identified ADAM17 as a direct target of miR-145. Collectively, these results suggest that as a tumor suppressor, miR-145 inhibits not only tumor proliferation, but also cell migration and invasion, and warrants further investigation.
Highlights
MicroRNAs are short single-stranded nucleotide RNA molecules, which function as master regulators of gene expression by post-transcriptional modifications of target mRNAs [1]
We found that ectopic expression of miR-145 in U87 and U251n glioma cells caused decreased proliferation, migration and invasion with accompanying low protein expression of ADAM17 and EGFR
In the present study we detected the miR-145 expression level in U87, U251n, T98G and HF66 human glioma cell lines, and found a significant reduction of miR-145 in human glioma cell lines compared to total RNA of frontal cortex
Summary
MicroRNAs (miRNAs) are short single-stranded nucleotide RNA molecules, which function as master regulators of gene expression by post-transcriptional modifications of target mRNAs [1]. The pattern of regulation of gene expression is sequence-specific. MiRNAs bind to 3' untranslated regions (3'-UTRs) of mRNAs and reduce the translation and/or stability of that mRNA, leading to a reduction in protein levels. Based on the unique feature of their targeting, miRNAs could have many targets [2], and, control a large number of proteins. MiRNAs may serve as either oncogenes or tumor suppressors [3,4]. The miR-145 is a tumor-suppressive miRNA [5] and its expression is low in different kinds of cancers. Mir-145 inhibits proliferation by targeting c-myc [6] and MUC1
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