MicroRNA-194 inhibits PRC1 activation of the Wnt/beta-catenin signaling pathway to prevent tumorigenesis by elevating self-renewal of non-side population cells and side population cells in esophageal cancer stem cells

摘要

Esophageal cancer (EC) is a leading cause of cancer-related deaths worldwide. Recent studies highlight roles for microRNAs (miRNAs) in EC. Microarray analysis identified miR-194 as downregulated in EC. However, little is known about the role of miR-194 in regulating self-renewal or other biological properties of EC stem cells. RT-qPCR and Western blot confirmed the downregulation of miR-194 in EC stem cells and revealed the upregulation of protein regulator of cytokinesis 1 (PRC1) in EC. Dual-luciferase reporter assay confirmed miR-194 targeting of PRC1 resulting in its downregulation. MiR-194 overexpression or PRC1 silencing reduced PRC1 expression, preventing the activation of the Wnt/beta-catenin signaling pathway. Inhibition of the Wnt/beta-catenin signaling pathway prevented the proliferation, invasion, and self-renewal of EC stem cells while promoting apoptosis. Furthermore, overexpressing miR-194 or silencing PRC1 in nude mice decreased the tumor formation ability of EC stem cells in vivo. Taken together, miR-194 prevents the progression of EC by downregulating PRC1 and inactivating the Wnt/beta-catenin signaling pathway.