Abstract
Recent comparative studies have indicated distinct expression profiles of short, non-coding microRNAs (miRNAs) in various types of cancer, including oral squamous cell carcinoma (OSCC). In this study, we employed a hybrid approach using Drosophila melanogaster as well as OSCC cell lines to validate putative targets of oral cancer-related miRNAs both in vivo and in vitro. Following overexpression of Drosophila miR-31, we found a significant decrease in the size of the imaginal wing discs and downregulation of a subset of putative targets, including wntless (wls), an important regulator of the Wnt signaling pathway. Parallel experiments performed in OSCC cells have also confirmed a similar miR-31-dependent regulation of human WLS that was not initially predicted as targets of human miR-31. Furthermore, we found subsequent downregulation of cyclin D1 and c-MYC, two of the main transcriptional targets of Wnt signaling, suggesting a potential role of miR-31 in regulating the cell cycle and proliferation of OSCC cells. Taken together, our Drosophila-based in vivo system in conjunction with the human in vitro platform will thus provide a novel insight into a mammal-to-Drosophila-to-mammal approach to validate putative targets of human miRNA and to better understand the miRNA-target relationships that play an important role in the pathophysiology of oral cancer.
Funder
National Research Foundation of Korea
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Cited by
9 articles.
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