Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 21, Issue 19, Pages -Publisher
MDPI
DOI: 10.3390/ijms21197232
Keywords
microRNA-31; Drosophila melanogaster; oral cancer; Wntless; Wnt pathway; mammal-to-Drosophila-to-mammal approach
Funding
- National Research Foundation of Korea (NRF) - Ministry of Science and ICT of Korea [NRF-2018R1A5A2023879, NRF-2015R1D1A1A02062399]
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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.
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