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

Abstract

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/β-catenin signaling pathway. Inhibition of the Wnt/β-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/β-catenin signaling pathway.

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Acknowledgements

We acknowledge and appreciate our colleagues for their valuable efforts and comments on this paper.

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Correspondence to Feng Miao.

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Animal experiments strictly abide by the relevant regulations of Guidance on Treating Experimental Animals released by the Ministry of Science and Technology of the People’s Republic of China, as well as the Guidelines for the Protection and Use of Laboratory Animals released by the National Institutes of Health (NIH) of the USA. Significant efforts were made to minimize both the number of animals used and their pain and suffering.

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Cai, S., Weng, Y. & Miao, F. MicroRNA-194 inhibits PRC1 activation of the Wnt/β-catenin signaling pathway to prevent tumorigenesis by elevating self-renewal of non-side population cells and side population cells in esophageal cancer stem cells. Cell Tissue Res (2021). https://doi.org/10.1007/s00441-021-03412-z

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Keywords

  • MicroRNA-194
  • Protein regulator cytokinesis 1
  • Esophageal cancer
  • Invasion
  • Migration
  • Proliferation
  • Self-renewal capacity