476 Differential regulation of miR-200b in squamous cell carcinoma of patients with recessive dystrophic epidermolysis bullosa
Journal of Investigative Dermatology(2022)
摘要
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.
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关键词
recessive dystrophic epidermolysis bullosa,squamous cell carcinoma
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