This study aims to investigate the degree of deregulation of tumor suppressor miR-200b in recessive dystrophic epidermolysis bullosa squamous cell carcinoma (RDEB-SCC) and to gain insight into whether and how miR-200b affects RDEB-SCC pathomechanisms. We hypothesize that miR-200b expression correlates with the epithelial-to-mesenchymal transition (EMT) state in RDEB-SCCs, and consequently, that the epithelial phenotype can be restored upon reintroduction of miR-200b. MiRNA expression profiling was performed on cultured RDEB-SCCs and -keratinocytes, with subsequent confirmation of deregulated miRNAs, including miR-200b, by TaqMan-qPCR. Cell morphology was classified as cobblestone or spindle-shaped using image cytometry. Further, mobility of RDEB-SCC cells was assessed by migration assay and supernatants of miR-200b overexpressing RDEB-SCC were used to treat endothelial cells (HUVEC) in an angiogenesis assay. A lower expression of miR-200b was observed in RDEB-SCCs, although to a varying extent between isolates from different tumor biopsies. Interestingly, RDEB-SCC cells exhibited morphological differences, varying between cobblestone- and spindle-shaped phenotypes, indicative of different stages in EMT, and low miR-200b-3p levels correlated with a mesenchymal phenotype and accelerated migration. Reintroduction of miR-200b-3p into RDEB-SCC cells resulted in a phenotype change towards epithelial and a significant attenuation in migration. Additionally, a reduction in tube formation capacity of HUVECs was observed upon exposure to supernatants of miR-200b overexpressing RDEB-SCCs. We show that the abundance of miR-200b negatively correlates with an aggressive, migratory phenotype of RDEB-SCCs, providing new insights into the malignancy of RDEB-SCCs. In addition, this miRNA might be a potential therapeutic target.

ESDR476 - Differential regulation of miR-200b in squamous cell carcinoma of patients with recessive dystrophic epidermolysis bullosa

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.