MicroRNA-31 Regulates Expression of Wntless in Both Drosophila melanogaster and Human Oral Cancer Cells

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.

Meta‐signature guided investigation of miRNA candidates as potential biomarkers of oral cancer

“…In addition, miR‐31 passenger strand regulates RhoA (Ras homolog family member A gene) expression, which leads to proliferation and migration of oral cancer cells (Chang et al, 2013). Proliferation and cell cycle of oral cancer cells is regulated by miR‐31 and its regulation of cyclin D1, c‐myc and WLS , important for Wnt signalling (Jung et al, 2020). As a putative target of miR‐31 in head and neck carcinoma was also identified NUMB gene, through which migration and invasion of cancer cells are facilitated (Chou et al, 2018).…”

Expression of miR-31 in saliva-liquid biopsy in patients with oral squamous cell carcinoma

“… 20 Recently, in vitro studies have suggested a potential role of miR-31 in regulating cell cycle and proliferation of OSCC tissues via Wnt and Hippo signalling pathways. 21 , 22 …”

Panoramic view of key cross-talks underpinning the oral squamous cell carcinoma stemness - unearthing the future opportunities

“…The potential targets of miR-31 were studied by Jung JE et al. ( 76 ), in Drosophila melanogaster and OSCC cell line models. The study confirmed the association of miR-31 in the maintenance of human Wntless mRNA, which is a key regulator of Wnt signaling.…”