Metastatic EMT Phenotype Is Governed by MicroRNA-200-Mediated Competing Endogenous RNA Networks

Epithelial-mesenchymal transition (EMT) is a fundamental physiologically relevant process that occurs during morphogenesis and organ development. In a pathological setting, the transition from epithelial toward mesenchymal cell phenotype is hijacked by cancer cells, allowing uncontrolled metastatic dissemination. The competing endogenous RNA (ceRNA) hypothesis proposes a competitive environment resembling a large-scale regulatory network of gene expression circuits where alterations in the expression of both protein-coding and non-coding genes can make relevant contributions to EMT progression in cancer. The complex regulatory diversity is exerted through an array of diverse epigenetic factors, reaching beyond the transcriptional control that was previously thought to single-handedly govern metastatic dissemination. The present review aims to unravel the competitive relationships between naturally occurring ceRNA transcripts for the shared pool of the miRNA-200 family, which play a pivotal role in EMT related to cancer dissemination. Upon acquiring more knowledge and clinical evidence on non-genetic factors affecting neoplasia, modulation of the expression levels of diverse ceRNAs may allow for the development of novel prognostic/diagnostic markers and reveal potential targets for the disruption of cancer-related EMT.

Automated summary

Epithelial-mesenchymal transition (EMT) is a fundamental physiological process in embryonic and organ development. In cancer, EMT is hijacked by cancer cells to promote uncontrolled metastatic dissemination. The competing endogenous RNA (ceRNA) hypothesis suggests that gene expression alterations, both coding and non-coding, contribute to EMT progression in cancer through a large-scale regulatory network. This regulatory diversity is exerted through various epigenetic factors beyond transcriptional control. This review aims to uncover the competitive relationships between ceRNA transcripts that share miRNA-200 family, which play a crucial role in EMT associated with cancer dissemination. Understanding the non-genetic factors influencing neoplasia and modulating the expression levels of various ceRNAs could lead to the development of novel prognostic/diagnostic markers and potential targets for disrupting cancer-related EMT.