miR-200c-3p regulates invasive capacity in human oral squamous cell carcinoma microenvironment

Recently, extracellular vesicles—particularly exosomes—have been recognized as intercellular communicators in the tumor microenvironment. As exosomic cargo, deregulated microRNAs (miRNAs) can shape the surrounding microenvironment in a cancer-dependent manner. Previous studies have shown inconsistent results regarding miR-200c-3p expression levels in OSCC cell lines, tissues, or serum—likely because of the heterogeneous characters of the specimen materials. For this reason, single-cell clone analyses are necessary to effectively assess the role of exosome-derived miRNAs on cells within the tumor microenvironment. In this study, we performed integrated microarray profiling to compare exosome-derived miRNA and exosome-treated cell-derived mRNA expression. Data were acquired from noninvasive SQUU-A and highly invasive SQUU-B tongue cancer cell clones derived from a single patient to determine candidate miRNAs that promote OSCC invasion. Matrigel invasion assays confirmed that hsa-miR-200c-3p was a key pro-invasion factor among six miRNA candidates. Consistently, silencing of the miR-200c-3p targets, CHD9 and WRN, significantly accelerated the invasive potential of SQUU-A cells. Thus, our data indicate that miR-200c-3p in exosomes derived from a highly invasive OSCC line can induce a similar phenotype in non-invasive counterparts.